AAPS - American Association of Pharmaceutical Scientists Focus Group - Protein Aggregation and Biological Consequences http://www.aapspharmaceutica.com/inside/focus_groups/ProteinAgg/index.asp Dear Colleague: The focus group steering committee, group members and, contributors are pleased to present our literature collection summary. Our goal is to provide you with a structured reference of published information to foster focused scientific discussions in the community around the topics of protein aggregation/particles and observations of unwanted reactions, especially immunogenicity. This collection is build, maintained, and expanded as a strictly voluntary effort for which we also kindly ask for your knowledgeable contributions through the literature collection portal on our website. The collection is structured according to the primary and secondary focus topic of the references as given in the table of contents. We hope you find this collection helpful. Abbreviations: phys. stress: physical stress; f-t: freeze-thaw AAPS Focus Group Aggregation and Biological Consequences Literature Collection Table of Contents 1 2 3 4 Aggregate/Particle and molecular structure 4 1.1 Aggregate/Particle and long-term storage 5 1.2 Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t 5 1.3 Aggregate/Particle detection/characterization 5 1.4 Immunogenicity observation - acute and/or sporadic 10 1.5 Immunogenicity observation - chronic and/or general 10 1.6 Immunogenicity assays 10 Aggregate/Particle and long-term storage 11 2.1 Aggregate/Particle and molecular structure 11 2.2 Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t 11 2.3 Aggregate/Particle detection/characterization 11 2.4 Immunogenicity observation - acute and/or sporadic 11 2.5 Immunogenicity observation - chronic and/or general 11 2.6 Immunogenicity assays 11 Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t 12 3.1 Aggregate/Particle and molecular structure 12 3.2 Aggregate/Particle and long-term storage 13 3.3 Aggregate/Particle detection/characterization 13 3.4 Immunogenicity observation - acute and/or sporadic 22 3.5 Immunogenicity observation - chronic and/or general 22 3.6 Immunogenicity assays 22 Aggregate/Particle detection/characterization 23 4.1 Aggregate/Particle and molecular structure 31 4.2 Aggregate/Particle and long-term storage 35 Page 2 of 46 Version 30 July 2010 AAPS Focus Group Aggregation and Biological Consequences Literature Collection 5 6 7 4.3 Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t 35 4.4 Immunogenicity observation - acute and/or sporadic 39 4.5 Immunogenicity observation - chronic and/or general 39 4.6 Immunogenicity assays 39 Immunogenicity observation - acute and/or sporadic 41 5.1 Aggregate/Particle and molecular structure 41 5.2 Aggregate/Particle and long-term storage 41 5.3 Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t 41 5.4 Aggregate/Particle detection/characterization 41 5.5 Immunogenicity observation - chronic and/or general 41 5.6 Immunogenicity assays 41 Immunogenicity observation - chronic and/or general 42 6.1 Aggregate/Particle and molecular structure 42 6.2 Aggregate/Particle and long-term storage 42 6.3 Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t 42 6.4 Aggregate/Particle detection/characterization 42 6.5 Immunogenicity observation - acute and/or sporadic 42 6.6 Immunogenicity assays 43 Immunogenicity assays 44 7.1 Aggregate/Particle and molecular structure 44 7.2 Aggregate/Particle and long-term storage 44 7.3 Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t 44 7.4 Aggregate/Particle detection/characterization 45 7.5 Immunogenicity observation - acute and/or sporadic 45 7.6 Immunogenicity observation - chronic and/or general 45 Page 3 of 46 Version 30 July 2010 AAPS Focus Group Aggregation and Biological Consequences Literature Collection Version 30 July 2010 1 Aggregate/Particle and molecular structure Data Source In vitro in vitro Substance Class Peptide Protein In vitro In vitro Protein Further substance classification / Substance name Corresponding author / Group head Title Kar Aromatic Interactions Promote SelfAssociation of Collagen Triple-Helical Peptides to Higher-Order Structures Chaperonin Apetri Chaperonin chamber accelerates protein folding through passive action of preventing aggregation Silica Radhakrishnan A Novel Route to Organic-Inorganic Hybrid Nanomaterials Collagen sphingomyelinases D In vitro In vitro Antibody In vivo animal In vitro Ig Liposome Protein prion protein Pires Structural insights into the catalytic mechanism of sphingomyelinases D and evolutionary relationship to glycerophosphodiester phosphodiesterases Benzyl (3-Acylaminopropyl) Dimethylammonium Chloride Surfactants: Structure and Some Properties of the Micellar Aggregates Kulahin Expression, crystallization and preliminary X-ray analysis of the extracellular Ig modules I-IV and F3 modules I-III of the neural celladhesion molecule L1 Whiteman Poly(HPMA)-coated liposomes demonstrate prolonged circulation in mice Lisa The structural intolerance of the PrP alpha-fold for polar substitution of the helix-3 methionines Murakami Page 4 of 46 Full citation K. Kar, S. Ibrar, V. Nanda, T. M. Getz, S. P. Kunapuli, B. Brodsky: Aromatic Interactions Promote Self-Association of Collagen Triple-Helical Peptides to Higher-Order Structures, Biochemistry 48(33): 7959-7968 (2009) A. C. Apetri, A. L. Horwich: Chaperonin chamber accelerates protein folding through passive action of preventing aggregation, Proceedings of the National Academy of Sciences 105(45): 17351-17355 (2008) B. Radhakrishnan, A. N. Constable, W. J. Brittain: A Novel Route to Organic-Inorganic Hybrid Nanomaterials, Macromolecular Rapid Communications 29(22): 1828-1833 (2009) M. T. Murakami, M. F. Fernandes-Pedrosa, S. A. de Andrade, A. Gabdoulkhakov, C. Betzel, D. V. Tambourgi, R. K. Arni: Structural insights into the catalytic mechanism of sphingomyelinases D and evolutionary relationship to glycerophosphodiester phosphodiesterases, Biochemical and Biophysical Research Communications 342(1): 323329 (2006) P. A. R. Pires, O. A. El Seoud: Benzyl (3-Acylaminopropyl) Dimethylammonium Chloride Surfactants: Structure and Some Properties of the Micellar Aggregates, Progress in Colloid and Polymer Science 133: 131-141 N. Kulahin, C. Kasper, O. Kristensen, J. S. Kastrup, V. Berezin, E. Bock, M. Gajhede: Expression, crystallization and preliminary X-ray analysis of the extracellular Ig modules I-IV and F3 modules I-III of the neural celladhesion molecule L1, Acta Crystallographica Section F 61: 858-860 (2005) K. R. Whiteman, V. Subr, K. Ulbrich, V. P. Torchilin: Poly(HPMA)-coated liposomes demonstrate prolonged circulation in mice, Journal of Liposome Research 11(2-3): 153-164 (2001) S. Lisa, M. Meli, G. Cabello, R. Gabizon, G. Colombo, M. Gasset: The structural intolerance of the PrP alpha-fold for polar substitution of the helix-3 methionines, Cellular and Molecular Life Sciences (May 2010) AAPS Focus Group Aggregation and Biological Consequences Literature Collection Version 30 July 2010 1.1 Aggregate/Particle and long-term storage N/A 1.2 Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t Data Source Substance Class Further substance classification / Substance name Corresponding author / Group head In vitro Protein Barstar Kumar Title Structurally Distinct Amyloid Protofibrils Form on Separate Pathways of Aggregation of a Small Protein Sanchez MDM4 binds ligands via a mechanism in which disordered regions become structured In vitro No experimental data No experimental data Protein MDM4, MDM2 In vitro Antibody IgG1 antibody Mahler H-C. In vitro Antibody IgG1 antibody Kiese Sylvia In vitro Protein In vitro Antibody Protein 0 Wang W. Protein 0 Wang W. 0 Strambini GB antibody IgG Hansson U. Protein aggregation and its inhibition in biopharmaceutics Instability, stabilization and formulation of liquid protein pharmaceuticals Induction and analysis of aggregates in a liuqid IgG1antibody formulation Shaken, not stirred: Mechanical Stress testing of an IgG1 antibody Proteins in frozen solutions: evidence of ice-induced partial unfolding Aggregation of human immunoglobulin G upon freezing Full citation S. Kumar, J. B. Udgaonkar: Structurally Distinct Amyloid Protofibrils Form on Separate Pathways of Aggregation of a Small Protein, Biochemistry 48(27): 6441-6449 (2009) M. C. Sanchez, J. G. Renshaw, G. Davies, P. N. Barlow, M. Vogtherr: MDM4 binds ligands via a mechanism in which disordered regions become structured, FEBS Letters 584(14): 3035-3041(2010) Wang W.: Protein aggregation and its inhibition in biopharmaceutics, Int. J .Pharm., 289: 1-30 (2005) Wang W.: Instability, stabilization and formulation of liquid protein pharmaceuticals, Int. J. Pharm.185: 129188; (1999) Mahler H.-C., Müller R., Frieß W., Delille A., Matheus S.: Induction and analysis of aggregates in a liuqid IgG1-antibody formulation, EJPB 59: 407-417 (2005) Kiese S., Pappenberger A., Friess W., Mahler H.-C.: Shaken, not stirred: Mechanical Stress testing of an IgG1 antibody, JPS: 1-20 (2007) Strambini G. B., Gabellieri E.: Proteins in frozen solutions: evidence of ice-induced partial unfolding, Biophys. J. 70: 971-976 (1996) Hansson U.: Aggregation of human immunoglobulin G upon freezing, Acta Chem. Scand., 22: 483-489 (1968) 1.3 Aggregate/Particle detection/characterization Data Source Further substance Substance classification / Class Substance name Corresponding author / Group head Title Full citation Page 5 of 46 AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro N- acetyl chitosan Hu In vitro Protein alphaA-crystallin Biswas In vitro Protein alphaB-crystallin Ecroyd poly(1,3cyclohexadiene) Natori In vitro In vitro Pires In vitro Protein alphaB-crystallin Santhoshkumar In vitro Protein betaA3-crystallin Gupta mRNA Niedzwiecka prion protein Frankenfield In vitro In vitro Protein Version 30 July 2010 Y. Hu, Y. Du, J. Yang, Y. Tang, J. Li, X. Wang: Self-aggregation and antibacterial activity of NSelf-aggregation and antibacterial activity of acylated chitosan, Polymer 48(11): 3098-3106 N-acylated chitosan (2007) A. Biswas, A. Miller, T. Oya-Ito, P. Santhoshkumar, M. Bhat, R. H. Nagaraj: Effect of Effect of site-directed mutagenesis of site-directed mutagenesis of methylglyoxalmethylglyoxal-modifiable arginine residues modifiable arginine residues on the structure and on the structure and chaperone function of chaperone function of human alphaA-crystallin, human alphaA-crystallin Biochemistry 45(14): 4569-4577 (2006) H. Ecroyd, S. Meehan, J. Horwitz, J.A. Aquilina, J.L.P. Benesch, C.V. Robinson, C.E. MacPhee, J.A. Carver: Mimicking phosphorylation of alphaBcrystallin affects its chaperone activity, The Mimicking phosphorylation of alphaBBiochemical Journal 401(1):129-141(2006) crystallin affects its chaperone activity I. Natori, H. Sato: Aggregation of poly(1,3cyclohexadiene): effects of molecular weight and Aggregation of poly(1,3-cyclohexadiene): polymer chain structure, Journal of Polymer effects of molecular weight and polymer Science Part B: Polymer Physics 44: 1442-1452 chain structure (2006) P. A. R. Pires, O. A. El Seoud: Surfactants with an amide group "spacer": Synthesis of 3Surfactants with an amide group "spacer": Synthesis of 3(acylaminopropyl)trimethylammonium chlorides and their aggregation in aqueous solutions, (acylaminopropyl)trimethylammonium chlorides and their aggregation in aqueous Journal of Colloid and Interface Science 304(2): 474-485 solutions P. Santhoshkumar, K. K. Sharma: Conserved F84 and P86 residues in alphaB-crystallin are Conserved F84 and P86 residues in alphaB- essential to effectively prevent the aggregation of crystallin are essential to effectively prevent substrate proteins, Protein Science 15(11): 2488the aggregation of substrate proteins 2498 (2006) R. Gupta, K. Srivastava, O. P. Srivastava: Truncation of motifs III and IV in human lens Truncation of motifs III and IV in human lens betaA3-crystallin destabilizes the structure, betaA3-crystallin destabilizes the structure Biochemistry 45(33): 9964-9978 (2006) A. Niedzwiecka, E. Darzynkiewicz, R. Stolarski: Deaggregation of elF4E Induced by mRNA 5' Cap Deaggregation of elF4E Induced by mRNA Binding, Nucleosides, Nucleotides, and Nucleic 5' Cap Binding Acids 24(5-7): 507-511 (2005) K. N. Frankenfield, E. T. Powers, J. W. Kelly: Influence of the N-terminal domain on the Influence of the N-terminal domain on the aggregation properties of the prion protein, Protein aggregation properties of the prion protein Science 14: 2154-2166 (2005) Page 6 of 46 AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro In vitro Copolymers Protein alphaB-crystallin Abbel Rod-Length Dependent Aggregation in a Series of Oligo(p-benzamide)-BlockPoly(ethylene glycol) Rod-Coil Copolymers Aquilina Phosphorylation of alphaB-crystallin alters chaperone function through loss of dimeric substructure In vitro Protein alpha-crystallin Horwitz The native oligomeric organization of alphacrystallin, is it necessary for its chaperone function? In vitro Protein prolactin Keeler The tertiary structure and backbone dynamics of human prolactin In vitro Protein Alpha-crystallin Horwitz Alpha-crystallin Erhardt Amphiphilic janus micelles with polystyrene and poly(methacrylic acid) hemispheres Gaylor Water-soluble conjugated oligomers: effect of chain length and aggregation on photoluminescence-quenching efficiencies Aydogan Comparison of the surface activity and bulk aggregation of ferrocenyl surfactants with cationic and anionic headgroups In vitro In vitro In vitro ferrocenyl surfactant Page 7 of 46 Version 30 July 2010 R. Abbel, T. W. Schleuss, H. Frey, A. F. M. Kilbinger: Rod-Length Dependent Aggregation in a Series of Oligo(p-benzamide)-BlockPoly(ethylene glycol) Rod-Coil Copolymers, Macromolecular Chemistry and Physics 206(20): 2067-2074 (2005) J. A. Aquilina, J. L. P. Benesch, L. L. Ding, O. Yaron, J. Horwitz, C. V. Robinson: Phosphorylation of alphaB-crystallin alters chaperone function through loss of dimeric substructure, Journal of Biological Chemistry 279(27): 28675-28680 (2004) J. Horwitz, Q. Huang, L. Ding: The native oligomeric organization of alpha-crystallin, is it necessary for its chaperone function? Experimental Eye Research 79(6): 817-821 (2004) C. Keeler, P. S. Dannies, M. E. Hodsdon: The tertiary structure and backbone dynamics of human prolactin, Journal of Molecular Biology 328(5): 1105-1121 (2003) J. Horwitz: Alpha-crystallin, Experimental Eye Research 76(2): 145-153 (2003) R. Erhardt, M. Zhang, A. Böker, H. Zettl, C. Abetz, P. Frederik, G. Krausch, V. Abetz, A. H. E. Mueller: Amphiphilic janus micelles with polystyrene and poly(methacrylic acid) hemispheres, Journal of American Chemical Society 125(11): 3260-3267 (2003) B. S. Gaylord, S. Want, A. J. Heeger, G. C. Bazan: Water-soluble conjugated oligomers: effect of chain length and aggregation on photoluminescence-quenching efficiencies, Journal of the American Chemical Society 123: 6417-6418 (2001) N. Aydogan, N. L. Abbott: Comparison of the surface activity and bulk aggregation of ferrocenyl surfactants with cationic and anionic headgroups, Langmuir 17(19): 5703-5706 (2001) AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro In vitro Peptid Protein Mong Beta-alanine-based dendritic beta-peptides: dendrimers possessing unusually strong binding ability towards protic solvents and their self-assembly into nanoscale aggregates through hydrogen-bond interactions Nakasako Tertiary and quaternary strucutres of photoreactive Fe-type nitrile hydratase from Rhodococcus sp. N-771: roles of hydration water molecules in stabilizing the strucutres and the structural origin of the substrate specificity of the enzyme Yu Multiple morphologies formed from an amphiphilic ABC triblock copolymer in solution Maruyama Nanoparticle DNA carrier with Poly(L-lysine) grafted polysaccharide copolymer and Poly(D,L-lactic acid) Calcitonin Costantino Development of Calcitonin Salmon Nasal Spray: Similarity of Peptide Formulated in Chlorobutanol Compared to Benzalkonium Chloride as Preservative Chlorhexidine Zeng Concentration dependent aggregation properties of chlorhexidine salts Walton The cavity-chaperone Skp protects its substrate from aggregation but allows independent folding of substrate domains dendritic betapeptides hydratase In vitro Copolymers In vitro polysaccaride copolymers In vitro Peptide In vitro In vitro Protein Skp Page 8 of 46 Version 30 July 2010 T. K.-K. Mong, A. Niu, H.-F. Chow, C. Wu, L. Li, R. Chen: Beta-alanine-based dendritic beta-peptides: dendrimers possessing unusually strong binding ability towards protic solvents and their selfassembly into nanoscale aggregates through hydrogen-bond interactions, Chemistry - A European Journal 7(3): 686-699 (2001) M. Nakasako, M. Odaka, M. Yohda, N. Dohmae, K. Takio, N. Kamiya, I. Endo: Tertiary and quaternary strucutres of photoreactive Fe-type nitrile hydratase from Rhodococcus sp. N-771: roles of hydration water molecules in stabilizing the strucutres and the structural origin of the substrate specificity of the enzyme, Biochemistry 38(31): 9887-9898 (1999) G. -E. Yu, A. Eisenberg: Multiple morphologies formed from an amphiphilic ABC triblock copolymer in solution 31 (16): Macromolecules: 5546–5549 (1998) A. Maruyama, T. Ishihara, J. -S. Kim, S. W. Kim, T. Akaike: Nanoparticle DNA carrier with Poly(Llysine) grafted polysaccharide copolymer and Poly(D,L-lactic acid), Bioconjugate Chemistry 8 (5): 735–742 (1997) H. R. Costantino, H. Culley, L. Chen, D. Morris, M. Houston, S. Roth, M. J. Phoenix, C. Foerder, J. S. Philo, T. Arakawa, L. Eidenschink, N. H. Andersen, G. Brandt, S. C. Quay: Development of Calcitonin Salmon Nasal Spray: Similarity of Peptide Formulated in Chlorobutanol Compared to Benzalkonium Chloride as Preservative, Journal of Pharmaceutical Science 98(10):3691-3706 (2009) P. Zeng, G. Zhang, A. Rao, W. Bowles, T. S. Wiedmann: Concentration dependent aggregation properties of chlorhexidine salts, International Journal of Pharmaceutics 367(1-2): 73-78 (2009) T. A. Walton, C. M. Sandoval, C. A. Fowler, A. Pardi, M. C. Sousa: The cavity-chaperone Skp protects its substrate from aggregation but allows independent folding of substrate domains, Proceedings of the National Academy of Sciences 106(6): 1772-1777 (2009) AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro In vitro Protein Protein beta2-Microglobulin Legumin Antonov Macromolecular complexes of the main storage protein of Vicia faba seeds with sulfated polysaccharide Poly(L-glutamic acid), Poly(Nisopropylacrylamide) He In vitro In vitro In vitro Eichner A Generic Mechanism of beta2Microglobulin Amyloid Assembly at Neutral pH Involving a Specific Proline Switch Novel Temperature- and pH-Responsive Graft Copolymers Composed of Poly(Lglutamic acid) and Poly(Nisopropylacrylamide) Liu Vesicular aggregation and morphologic evolvement of a flexible-rigid block hydrogen-bonding complex Hwang Interruptions in the collagen repeating tripeptide pattern can promote supramolecular association Protein Collagen In vitro Peptide nucleic acidcontaining nanoparticles Bartlett Physicochemical and biological characterization of targeted, nucleic acidcontaining nanoparticles In vitro Protein Ure2 Perrett Equilibrium folding properties of the yeast prion protein determinant Ure2 protein therapeutics Tatford O.C. Analytical techniques for the evaluation of liquid protein therapeutics No experimental data Protein Please select Protein 0 Fink, A.L. Protein aggregation: folding aggregates, inclusion bodies and amyloid Page 9 of 46 Version 30 July 2010 T. Eichner, S. E. Radford: A Generic Mechanism of beta2-Microglobulin Amyloid Assembly at Neutral pH Involving a Specific Proline Switch, Journal of Molecular Biology 386(5): 1312-1326 (2009) Y. A. Antonov, T. Sato: Macromolecular complexes of the main storage protein of Vicia faba seeds with sulfated polysaccharide, Food Hydrocolloids 23(3): 996-1006 (2009) C. He, C. Zhao, X. Guo, Z. Guo, X. Chen, X. Zhuang, S. Liu, X. Jing: Novel Temperature- and pH-Responsive Graft Copolymers Composed of Poly(L-glutamic acid) and Poly(Nisopropylacrylamide), Journal of Polymer Science, Part A: Polymer Chemistry 46(12): 4140-4150 (2008) Q. Liu, Y. Wang, W. Li, L. Wu: Vesicular aggregation and morphologic evolvement of a flexible-rigid block hydrogen-bonding complex, Polymer 49(19): 4159-4167 (2008) E. S. Hwang, G. Thiagarajan, A. S. Parmar, B. Brodsky: Interruptions in the collagen repeating tripeptide pattern can promote supramolecular association, Protein Science 19(5): 1053-1064 (2010) D. W. Bartlett, M. E. Davis: Physicochemical and biological characterization of targeted, nucleic acid-containing nanoparticles, Bioconjugate Chemistry 18 (2): 456–468 (2007) S. Perrett, S. J. Freeman, P. J. G. Butler, A. R. Fersht: Equilibrium folding properties of the yeast prion protein determinant Ure2, Journal of Molecular Biology 290 (1): 331-345 (1999) Tatford O.C.; Gomme P.T. and Bertolini J.: Analytical techniques for the evaluation of liquid protein therapeutics, Biotechnol. Appl. Biochem Nr. 40: 67-81 (2004) Fink, A.L.: Protein aggregation: folding aggregates, inclusion bodies and amyloid. Fold Des. 3 : R9 - R23, 1998 AAPS Focus Group Aggregation and Biological Consequences Literature Collection 1.4 Immunogenicity observation - acute and/or sporadic N/A 1.5 Immunogenicity observation - chronic and/or general N/A 1.6 Immunogenicity assays N/A Page 10 of 46 Version 30 July 2010 AAPS Focus Group Aggregation and Biological Consequences Literature Collection Version 30 July 2010 2 Aggregate/Particle and long-term storage 2.1 Aggregate/Particle and molecular structure N/A 2.2 Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t N/A 2.3 Aggregate/Particle detection/characterization N/A 2.4 Immunogenicity observation - acute and/or sporadic N/A 2.5 Immunogenicity observation - chronic and/or general Data Source In vivo animal Substance Class Further substance classification / Substance name Corresponding author / Group head influenza vaccines Kim Title Stability Kinetics of Influenza Vaccine Coated onto Microneedles During Drying and Storage 2.6 Immunogenicity assays N/A Page 11 of 46 Full citation Y.-C. Kim, F.-S. Quan, R. W. Compans, S.-M. Kang, M. R. Prausnitz: Stability Kinetics of Influenza Vaccine Coated onto Microneedles During Drying and Storage, Pharmaceutical Research (April 2010) AAPS Focus Group Aggregation and Biological Consequences Literature Collection Version 30 July 2010 3 Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t Data Source In vitro Substance Class Further substance classification / Substance name Protein Lactoferrin, ßLactoglobulin In vitro In vitro Corresponding author / Group head Title Sarkar Colloidal stability and interactions of milk-protein-stabilized emulsions in an artificial saliva Seidler Protein alpha- synuclein Munishkina Identification and prediction of promiscuous aggregating inhibitors among known drugs Conformational behavior and aggregation of alpha-synuclein in organic solvents: modeling the effects of membranes Full citation A. Sarkar, K. K. T. Goh, H. Singh: Colloidal stability and interactions of milk-protein-stabilized emulsions in an artificial saliva, Food Hydrocolloids 23(5): 1270-1278 (2009) J. Seidler, S. L. McGovern, T. N. Doman, B. K. Shoichet: Identification and prediction of promiscuous aggregating inhibitors among known drugs, Journal of Medicinal Chemistry 46(21): 4477-4486 (2003) L. A. Munishkina, C. Phelan, V. N. Uversky, A. L. Fink: Conformational behavior and aggregation of alphasynuclein in organic solvents: modeling the effects of membranes, Biochemistry 42(9): 2720-2730 (2003) 3.1 Aggregate/Particle and molecular structure Data Source Substance Class Further substance classification / Substance name Corresponding author / Group head In vitro Protein Vicilin Tang In vitro Peptide Amyloid Varela In vitro Protein alpha- Amylase Olsen Title Full citation C.-H. Tang, L. Chen, C.-Y. Ma: Thermal aggregation, amino acid composition and in vitro digestibility of vicilinThermal aggregation, amino acid rich protein isolates from three Phaseolus legumes: A composition and in vitro digestibility of comparative study, Food Chemistry 113(4): 957-963 vicilin-rich protein isolates from three Phaseolus legumes: A comparative study (2009) A single mutation in an SH3 domain L. Varela, B. Morel, A. I. Azuaga, F. Conejero-Lara: A increases amyloid aggregation by single mutation in an SH3 domain increases amyloid accelerating nucleation, but not by aggregation by accelerating nucleation, but not by destabilizing thermodynamically the destabilizing thermodynamically the native state, FEBS native state Letters 583(4): 801-806 (2009) S. N. Olsen, K. B. Andersen, T. W. Randolph, J. F. Carpenter, P. Westh: Role of electrostatic repulsion on Role of electrostatic repulsion on colloidal colloidal stability of Bacillus halmapalus alpha-amylase, stability of Bacillus halmapalus alphaBiochimica et Biophysica Acta (BBA) - Proteins & amylase Proteomics 1794(7): 1058-1065 (2009) Page 12 of 46 AAPS Focus Group Aggregation and Biological Consequences Literature Collection Version 30 July 2010 3.2 Aggregate/Particle and long-term storage Data Source Substance Class In vitro in vitro Protein In vitro Further substance classification / Substance name Corresponding author / Group head AAV2 Wright recombinant Human Flt3 Ligand Remmele Jr. AAV2 Wright Title Full citation J. F. Wright, T. Le, J. Prado, J. Bahr-Davidson, P. H. Smith, Z. Identification of factors that contribute Zhen, J. M. Sommer, G. F. Pierce, G. Qu: Identification of to recombinant AAV2 particle factors that contribute to recombinant AAV2 particle aggregation and methods to prevent aggregation and methods to prevent its occurrence during its occurrence during vector vector purification and formulation, Molecular Therapy 12(1): 171-178 (2005) purification and formulation Minimization of recombinant Human R. L. Remmele Jr., S. D. Bhat, D. H. Phan, W. R. Gombotz: Flt3 Ligand Aggregation at the Tm Minimization of recombinant Human Flt3 Ligand Aggregation plateau: A matter of thermal at the Tm plateau: A matter of thermal reversibility, reversibility Biochemistry 38(16): 5241-5247 (1999) J. F. Wright, T. Le, J. Prado, J. Bahr-Davidson, P. H. Smith, Z. Identification of factors that contribute Zhen, J. M. Sommer, G. F. Pierce, G. Qu: Identification of factors that contribute to recombinant AAV2 particle to recombinant AAV2 particle aggregation and methods to prevent aggregation and methods to prevent its occurrence during vector purification and formulation, Molecular Therapy 12(1): its occurrence during vector purification and formulation 171-178 (2005) 3.3 Aggregate/Particle detection/characterization Data Source In vitro In vitro In vitro Substance Class Antibody Protein Protein Further substance classification / Substance name Antibody IgG Lysozyme soy protein Corresponding author / Group head Title Hawe Structural properties of monoclonal antibody aggregates induced by freezethawing the thermal stress Bangali Biospecific Protein Immobilization for Rapid Analysis of Weak Protein Interactions Using Self-Interaction Nanoparticle Spectroscopy Tang Effect of high pressure treatment on aggregation and structural properties of soy protein isolate Page 13 of 46 Full citation A. Hawe, J. C. Kasper, W. Friess, W. Jiskoot: Structural properties of monoclonal antibody aggregates induced by freeze-thawing the thermal stress, European Journal of Pharmaceutical Sciences 38(2): 79-87 (2009) A. N. Bengali, P. M. Tessier: Biospecific Protein Immobilization for Rapid Analysis of Weak Protein Interactions Using Self-Interaction Nanoparticle Spectroscopy, Biotechnology and Bioengineering 104 (2): 240-250 (2009) C.-H. Tang, C.-Y. Ma: Effect of high pressure treatment on aggregation and structural properties of soy protein isolate, LWT - Food Science and Technology 42 (2): 606-611 (2009) AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro Protein In vitro In vitro Antibody In vitro α-lactalbumin McGuffrey Methylcellulose Funami HBsAg Li Copolymer Xu In vitro Protein In vitro Protein Amyloid In vitro Protein β- Lactoglobulin Akkermans In vitro Protein Interferon- tau Katayama In vitro Tjernberg Lambeth Version 30 July 2010 M. K. McGuffey, D. E. Otter, J. H. van Zanten, E. A. Foegeding: Solubility and aggregation of commercial Solubility and aggregation of commercial alpha-lactalbumin at neutral pH, International Dairy alpha-lactalbumin at neutral pH Journal 17(10): 1168-1178 (2007) T. Funami, Y. Kataoka, M. Hiroe, I. Asai, R. Takahashi, K. Nishinari: Thermal aggregation of Thermal aggregation of methylcellulose methylcellulose with different molecular weights, Food with different molecular weights Hydrocolloids 21(1): 46-58 (2007) Y. Li, J. Bi, W. Zhou, Y. Huang, L. Sun, A.-P. Zeng, G. Ma, Z. Su: Characterization of the large size Characterization of the large size aggregation of Hepatitis B virus surface aggregation of Hepatitis B virus surface antigen (HBsAg) formed in ultrafiltration process, Process antigen (HBsAg) formed in ultrafiltration process Biochemistry 42(3): 315-319 (2007) Y. Xu, L. Shi, R. Ma, W. Zhang, Y. An, X. X. Zhu: Synthesis and micellization of thermo-and Synthesis and micellization of thermo-and pHpH-responsive block copolymer of poly(N- responsive block copolymer of poly(Nisopropylacrylamide)-block-poly(4-vinylpyridine), isopropylacrylamide)-block-poly(4vinylpyridine) Polymer 48(6): 1711-1717 (2007) A. Tjernberg, N. Markova, W. J. Griffiths, D. Hallén: DMSO-related effects in protein characterization, DMSO-related effects in protein Journal of Biomolecular Screening 11: 131-137 characterization (2006) B. Morel, S. Casares, F. Conejero-Lara: A Single Mutation Induces Amyloid Aggregation in the αA Single Mutation Induces Amyloid Aggregation in the α-Spectrin SH3 Spectrin SH3 Domain: Analysis of the Early Stages of Fibril Formation, Journal of Molecular Biology 356(2): Domain: Analysis of the Early Stages of Fibril Formation 453-468 (2006) C. Akkermans, P. Venema, S. S. Rogers, A. J. van der Goot, R. M. Boom, E. van der Linden: Shear Pulses Nucleate Fibril Aggregation, Food Biophysics Shear Pulses Nucleate Fibril Aggregation 1(3): 144-150 (2006) D. S. Katayama, R. Nayar, D. K. Chou, J. J. Valente, J. Cooper, C. S. Henry, D. G. Vander Velde, L. Villarete, C. P. Liu, M. C. Manning: Effect of Buffer Species on the Thermally Induced Aggregation of Effect of Buffer Species on the Thermally Interferon-tau, Journal of Pharmaceutical Sciences Induced Aggregation of Interferon-tau 95(6): 1212-1226 (2006) R. H. Lambeth, S. Ramakrishnan, R. Mueller, J. P. Poziemsky, G. S. Miguel, L. J. Markoski, C. F. Zukoski, J. S. Moore: Synthesis and aggregation behavior of thermally responsive star polymers, Synthesis and aggregation behavior of thermally responsive star polymers Langmuir 22(14): 6352-6360 (2006) Page 14 of 46 AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro Protein buckwheat globulin Choi In vitro Protein Amyloid-beta(1-40) Rangachari In vitro Protein Heat shock proteins Cashikar In vitro Protein bovine α-lactalbumin Otte Xyloglucan Freitas In vitro In vitro Protein alpha-synuclein Uversky In vitro Protein carbonic anhydrase Nomura NNRTI Frenkel Simulated data Version 30 July 2010 S.-M. Choi, C.-Y. Ma: Study of thermal aggregation of globulin from common buckwheat (Fagopyrum Study of thermal aggregation of globulin esculentum Moench) by size-exclusion from common buckwheat (Fagopyrum chromatography and laser light scattering, Journal of esculentum Moench) by size-exclusion Agricultural and Food Chemistry 54(2): 554-561 chromatography and laser light scattering (2006) V. Rangachari, D. K. Reed, B. D. moore, T. L. Rosenberry: Secondary structure and interfacial Secondary structure and interfacial aggregation of amyloid-beta(1-40) on sodium dodecyl aggregation of amyloid-beta(1-40) on sulfate micelles, Biochemistry 45(28): 8639-8648 sodium dodecyl sulfate micelles (2006) A. G. Cashikar, M. Duennwald, S. L. Lindquist: A chaperone pathway in protein disaggregation: hsp26 A chaperone pathway in protein disaggregation: hsp26 alters the nature of alters the nature of protein aggregates to facilitate reactivation by hsp104s, Journal of Biological protein aggregates to facilitate Chemistry 280(25): 23869-23875 reactivation by hsp104s J. Otte, R. Ipsen, R. Bauer, M. J. Bjerrum, R. Waninge: Formation of amyloid-like fibrils upon Formation of amyloid-like fibrils upon limited proteolysis of bovine α-lactalbumin, limited proteolysis of bovine α-lactalbumin International Dairy Journal 15(3): 219-229 (2005) R. A. Freitas, S. Martin, G. L. Santos, F. Valenga, M. S. Buckeridge, F. Reicher, M.-R. Sierakowski: Physico-chemical properties of seed xyloglucans from different sources, Carbohydrate Polymers 60: 507Physico-chemical properties of seed 514 (2005) xyloglucans from different sources V. N. Uversky, G. Yamin, L. A. Munishkina, M. A. Karymov, I S. Millett, S. Doniach, Y. L. Lyubchenko, A. L. Fink: Effects of nitration on the structure and aggregation of alpha-synuclein, Molecular Brain Effects of nitration on the structure and Research 134: 84-102 (2005) aggregation of alpha-synuclein Y. Nomura, Y. Sasaki, M. Takagi, T. Narita, Y. Thermoresponsive controlled association Aoyama, K. Akiyoshi: Thermoresponsive controlled of protein with a dynamic nanogel of association of protein with a dynamic nanogel of hydrophobized polysaccharide and cyclodextrin: heat hydrophobized polysaccharide and cyclodextrin: heat shock protein-like shock protein-like activity of artificial molecular chaperone, Biomacromolecules 6(1): 447-452 (2005) activity of artificial molecular chaperone Y. V. Frenkel, A. D. Clark, Jr., K. Das, Y.-H. Wang, P. J. Lewi, P. A. J. Janssen, E. Arnold: Concentration Concentration and pH dependent and pH dependent aggregation of hydrophobic drug aggregation of hydrophobic drug molecules and relevance to oral bioavailability, molecules and relevance to oral Journal of Medicinal Chemistry 48(6): 1974-1983 bioavailability (2005) Page 15 of 46 AAPS Focus Group Aggregation and Biological Consequences Literature Collection maltodxtrin, isoamylase In vitro In vitro In vitro In vitro metallofullerene Protein Protein Malate dehyrogenase sophoragrin Pohu Split crystallization during debranching of maltodextrins at high concentration by isoamylase Sitharaman Gd@C60[C(COOH)2]10 and Gd@C60(OH)X: nanoscale aggregation studies of two metallofullerene MRI contrast agents in aqueous solution Schlieker Solubilization of aggregated proteins by ClpB/DnaK relies on the continuous extraction of unfolded polypeptides Ueda Solubility-insolubility interconversion of sophoragrin, a mannose/glucose-specific lectin in sophora japonica (Japanese pagoda tree) bark, regulated by the sugar-specific interaction In vitro Protein whey protein de la Fuente Influence of kappa-carrageenan on the aggregation behaviour of proteins in heated whey protein isolate solutions In vitro Protein oat globulin Zhao Study of thermal aggregation of oat globulin by laser light scattering Mogk Refolding of substrates bound to small Hsps relies on a disaggregation reaction mediated most efficiently by ClpB/DnaK Picout Pressure cell assisted solubilization of xyloglucans: tamarind seed polysaccharide and detarium gum Andya Mechanisms of aggregate formation and carbohydrate excipient stabilization of lyophilized humanized monoclonal antibody formulations In vitro Protein In vitro In vitro polysaccaride Antibody Page 16 of 46 Version 30 July 2010 A. Pohu,V. Planchot, J. L. Putaux, P. Colonna, A. Buléon: Split crystallization during debranching of maltodextrins at high concentration by isoamylase, Biomacromolecules 5(5): 1792-1798 (2004) B. Sitharaman, R. D. Bolskar, I. Rusakova, L. J. Wilson: Gd@C60[C(COOH)2]10 and Gd@C60(OH)X: nanoscale aggregation studies of two metallofullerene MRI contrast agents in aqueous solution, Nano Letters 4(12): 2373-2378 (2005) C. Schlieker, I. Tews, B. Bukau, A. Mogk: Solubilization of aggregated proteins by ClpB/DnaK relies on the continuous extraction of unfolded polypeptides, FEBS Letters 578(3): 351-356 (2005) H. Ueda, H. Fukushima, Y. Hatanaka, H. Ogawa: Solubility-insolubility interconversion of sophoragrin, a mannose/glucose-specific lectin in sophora japonica (Japanese pagoda tree) bark, regulated by the sugarspecific interaction, Biochemical Journal 382(Pt 3): 821-829 (2004) M.A. de la Fuente, Y. Hemar, H. Singh: Influence of kappa-carrageenan on the aggregation behaviour of proteins in heated whey protein isolate solutions, Food Chemistry 86(1): 1-9 (2004) Y. Zhao, Y. Mine, C.-Y. Ma: Study of thermal aggregation of oat globulin by laser light scattering, Journal of Agricultural Food Chemistry 52(10): 30893096 (2004) A. Mogk, C. Schlieker, K. L. Friedrich, H.-J. Schönfeld, E. Vierling, B. Bukau: Refolding of substrates bound to small Hsps relies on a disaggregation reaction mediated most efficiently by ClpB/Dank, Journal of Biological Chemistry 278(33): 31033-31042 (2003) D. R. Picout, S. B. Ross-Murphy, N. Errington, S. E. Harding: Pressure cell assisted solubilization of xyloglucans: tamarind seed polysaccharide and detarium gum, Biomacromolecules 4(3): 799807(2003) J. D. Andya, C. C. Hsu, S. J. Shire: Mechanisms of aggregate formation and carbohydrate excipient stabilization of lyophilized humanized monoclonal antibody formulations, AAPS PharmSci 5(2): 1-11 (2003) AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro Copolymer Yamauchi In vitro Protein Whey Kazmierski In vitro Protein ovalbumin Weijers copolymer Pispas In vitro In vitro Protein Subtilisin Pan In vitro Peptid colony stimulating factor Bartkowski In vitro Protein gelatine Tromp guar gum Picout In vitro In vitro Protein Thaumatin Iulek In vitro Protein sHsp Usui Version 30 July 2010 K. Yamauchi, J. R. Lizotte, T. E. Long: Thermoreversibile poly(alkyl acrylates) consisting of self-complimentary multiple hydrogen bonding, Macromolecules 36(4): 1083-1088 (2003) M. Kazmierski, M. Corredig: Characterization of soluble aggregates from whey protein isolate, Food Characterization of soluble aggregates from whey protein isolate Hydrocolloids 17(5): 685-692 (2003) M. Weijers, P. A. Barneveld, M. A. C. Stuart, R. W. Visschers: Heat-induced denaturation and Heat-induced denaturation and aggregation of ovalbumin at neutral pH described by aggregation of ovalbumin at neutral pH irreversible first-order kinetics, Protein Science described by irreversible first-order 12(12): 2693-703 (2003) kinetics Aggregation behavior of poly(butadieneS. Pispas, N. Hadjichristidis: Aggregation behavior of b-ethylene oxide) block copolymers in poly(butadiene-b-ethylene oxide) block copolymers in dilute aqueous solutions: effect of dilute aqueous solutions: effect of concentration, concentration, temperature, ionic temperature, ionic strength, and type of surfactant, strength, and type of surfactant Langmuir 19(1): 48-54 (2003) X. Pan, C. E. Glatz: Solvent effects on the second virial coefficient of subtilisin and solubility, Crystal Solvent effects on the second virial coefficient of subtilisin and solubility Growth and Design 3(2): 203-207 (2003) R. Bartkowski, R. Kitchel, N. Peckham, L. Margulis: Aggregation of recombinant bovie granulocyte colony Aggregation of recombinant bovie granulocyte colony stimulating factor in stimulating factor in solution, Journal of Protein Chemistry 21(3): 137-143 (2002) solution R. H. Tromp, E. ten Grotenhuis, C. Olieman: Selfaggregation of gelatine above the gelling temperature Self-aggregation of gelatine above the gelling temperature analysed by SECanalysed by SEC-MALLS, Food Hydrocolloids 16(3): 235-239 (2002) MALLS D. R. Picout, S. B. Ross-Murphy, N. Errington, S. E. Pressure cell assisted solution Harding: Pressure cell assisted solution characterization of polysaccharides. 1. Guar gum, characterization of polysaccharides. 1. Guar gum Biomacromolecules 2(4): 1301-1309 (2001) J. Iulek, A. M. Carcamo: The influence of precipitant The influence of precipitant and thaumatin and thaumatin concentration on the protein concentration on the protein aggregation aggregation state at low ionic strengths, Publicatio UEPG - Biological and Health Science 7(1): 91-98 state at low ionic strengths Small heat shock proteins of a K. Usui, T. Yoshida, T. Maruyama, M. Yohda: Small hyperthermophilic archaeum, heat shock proteins of a hyperthermophilic archaeum, Thermococcus sp. Strain KS-1, Exists as Thermococcus sp. Strain KS-1, Exists as a spherical a spherical 24 mer and its expression is 24 mer and its expression is highly induced under highly induced under heat-stress heat-stress conditions, Journal of Bioscience and conditions Bioengineering 92(2): 161-166 (2001) Thermoreversibile poly(alkyl acrylates) consisting of self-complimentary multiple hydrogen bonding Page 17 of 46 AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro In vitro In vitro In vitro In vitro In vitro Cyclodextrin Protein beta-lactoglobulin Protein beta-lactoglobulin Protein beta-, alphalactoglobulin Protein Protein In vitro bovine serum albumin Beta- lactoglobulin Aeromonas gum Sharma Influence of cylodextrin ring substituents on folding-related aggregation of bovine carbonic anhydrase Carrotta Conformational characterization of oligomeric intermediates and aggregates in beta-lactoglobulin heat aggregation Schokker Heat-induced aggregation of betalactoglobulin AB at pH 2.5 as influenced by ionic strength and protein concentration Schokker Heat-induced aggregation of betalactoglobulin A and B with alphalactalbumin Nishimura Aggregation behaviour of bovine serum albumin as a cause of sauce liquid separation by heating Bauer Characterization and isolation of intermediates in beta-lactoglobulin heat aggregation at high pH Xu Aggregation and disaggregation of Aeromonas gum in an aqueous solution under different conditions In vitro Protein beta-lactoglobulin Schokker Characterization of intermediates formed during heat-induced aggregation of betalactoglobulin AB at neutral pH In vitro Protein Rnase, human serum albumin Sah Protein Behavior at the Water/Methylene Chloride Interface In vitro Protein beta-lactoglobulin Hoffmann Heat-induced aggregation of betalactoglobulin as a function of pH Page 18 of 46 Version 30 July 2010 L. Sharma, A. Sharma: Influence of cylodextrin ring substituents on folding-related aggregation of bovine carbonic anhydrase, Euopean Journal of Biochemistry 268(8): 2456-2463 (2001) R. Carrotta, R. Bauer, R. Waninge, C. Rischel: Conformational characterization of oligomeric intermediates and aggregates in beta-lactoglobulin heat aggregation, Protein Science 10(7): 1312-1318 (2001) E. P. Schokker, H. Singh, D. N. Pinder, L. K. Creamer: Heat-induced aggregation of betalactoglobulin AB at pH 2.5 as influenced by ionic strength and protein concentration, International Dairy Journal 10(4): 233-240 (2000) E. P. Schokker, H. Singh, L. K. Creamer: Heatinduced aggregation of beta-lactoglobulin A and B with alpha-lactalbumin, International Dairy Journal 10(12): 843-853 (2000) K. Nishimura, M. Goto, T. Higasa, S. Kawase, Y. Matsumura: Aggregation behaviour of bovine serum albumin as a cause of sauce liquid separation by heating, Journal of the Science of Food and Agriculture 81(1): 76-81 (2001) R. Bauer, R. Carrotta, C. Rischel, L. Øgendal: Characterization and isolation of intermediates in beta-lactoglobulin heat aggregation at high pH, Biophysical Journal 79(2): 1030-1038 (2000) X. Xu, L. Zhang: Aggregation and disaggregation of Aeromonas gum in an aqueous solution under different conditions, Journal of Polymer Science: Part B: Polymer Physics 38(20): 2644-2651 (2000) E. P. Schokker, H. Singh, D. N. Pinder, G. E. Norris, L. K. Creamer: Characterization of intermediates formed during heat-induced aggregation of betalactoglobulin AB at neutral pH, International Dairy Journal 9(11): 791-800 (1999) H. Sah: Protein Behavior at the Water/Methylene Chloride Interface, Journal of Pharmaceutical Sciences 88(12): 1320-1325 (1999) M. A. M. Hoffmann, P. J. J. M. van Mil: Heat-induced aggregation of beta-lactoglobulin as a function of pH, Journal of Agricultural and Food Chemistry 47(5): 1898-1905 (1999) AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro Protein mannitol permease Broos A mechanism to alter reversibly the oligomeric state of a membrane-bound protein demonstrated with Escherichia coli EIImtl in solution In vitro Protein beta-lactoglobulin Bauer Detection of intermediate oligomers, important for the formation of heat aggregates of beta-lactoglobulin In vitro Protein beta-lactoglobulin Hoffmann Molecular mass distributions of heatinduced beta-lactoglobulin aggregates Protein Lysozyme Kuwamoto Radiation damage to a protein solution, detected by synchrotron X-ray smallangle scattering: dose-related considerations and suppression by cryoprotectants In vitro Protein phytase, acid phosphatase GrueningerLeitch Deglycosylation of proteins for crystallization using recombinant fusion protein glycosidases in vitro Protein egg white Mine Effect of pH during the dry heating on the gelling properties of egg white proteins Zhang A new strategy for enhancing the stability of lyophilized protein: The effect of the reconstitution Medium on keratinocyte growth factor In vitro Protein keratinocytegrowth factor In vitro Antibody monoclonal IgM antigroup B Streptococcus antibody Gombotz The stabilization of a human IgM monoclonal antibody with poly(vinlypyrrolidone) In vitro Antibody IgG Bee Response of a Concentrated Monoclonal Antibody Formulation to High Shear In vitro Page 19 of 46 Version 30 July 2010 J. Broos, R. T. Hoeve-Duurkens, G. T. Robillard: A mechanism to alter reversibly the oligomeric state of a membrane-bound protein demonstrated with Escherichia coli EIImtl in solution, Journal of Biological Chemistry 273(7): 3865-3870 (1998) R. Bauer, S. Hansen, L. Øgendal: Detection of intermediate oligomers, important for the formation of heat aggregates of beta-lactoglobulin, International Dairy Journal 8(2): 105-112 (1998) M. A. M. Hoffmann, G. Sala, C. Olieman, K. G. de Kruif: Molecular mass distributions of heat-induced beta-lactoglobulin aggregates, Journal of Agricultural and Food Chemistry 45 (8): 2949–2957 (1997) S. Kuwamoto, S. Akiyama, T. Fujisawa: Radiation damage to a protein solution, detected by synchrotron X-ray small-angle scattering: dose-related considerations and suppression by cryoprotectants, Journal of Synchrotron Radiation 11(6): 462-468 (1997) F. Grueninger-Leitch, A. D'Arcy, B. D'Arcy, C. ChèneDeglycosylation of proteins for crystallization using recombinant fusion protein glycosidases, Protein Science 5(12): 2617–2622 (1996) Y. Mine: Effect of pH during the dry heating on the gelling properties of egg white proteins, Food Research International 29(2): 155-161 (1996) M. Z. Zhang, J. Wen. T. Arakawa, S. J. Prestrelski: A new strategy for enhancing the stability of lyophilized protein: The effect of the reconstitution Medium on keratinocyte growth factor, Pharmaceutical Research 12(10): 1447-1452 (1995) W. R. Gombotz, S. C. Pankey, D. Phan, R. Drager, K. Donaldson, K. P. Antonsen, A. S. Hoffman, H. V. Raff: The stabilization of a human IgM monoclonal antibody with poly(vinlypyrrolidone), Pharmaceutical Research 11(5): 624-632 (1994) J. S. Bee, J. L. Stevenson, B. Mehta, J. Svitel, J. Pollastrini, R. Platz, E. Freund, J. F. Carpenter, T. W. Randolph: Response of a Concentrated Monoclonal Antibody Formulation to High Shear, Biotechnology and Bioengineering 103(5): 936-943 (2009) AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro Protein Whey protein Flett In vitro Protein Soy protein Keerati-u-rai in vitro Sulfobetain Che In vitro zero-valent iron Tiraferri beta- lactoglobulin, alpha- lactoglobulin Vardhanabhuti In vitro Protein In vitro Protein In vitro Peptid In vitro Protein Salgado In vitro Protein Salgado In vitro Protein Coan Amyloid Abeta BSA Bateman Bagger Version 30 July 2010 K. L. Flett, M. Corredig: Whey protein aggregate formation during heating in the presence of KWhey protein aggregate formation during carrageenan, Food chemistry 115(4): 1479-1485 heating in the presence of K-carrageenan (2009) M. Keerati-u-rai, M. Corredig: Effect of Dynamic High Pressure Homogenization on the Aggregation State Effect of Dynamic High Pressure Homogenization on the Aggregation State of Soy Protein, Journal of Agricultural and Food Chemistry 57(9): 3556-3562 (2009) of Soy Protein Y.-J. Che, Y. Tan, J. Cao, G.-Y. Xu: A study of aggregation behavior of a sulfobetaine copolymer in A study of aggregation behavior of a dilute solution, Journal of Polymer Research: online sulfobetaine copolymer in dilute solution (2009) A. Tiraferri, K. L. Chen, R. Sethi, M. Elimelech: Reduced aggregation and sedimentation of zeroReduced aggregation and sedimentation valent iron nanoparticles in the presence of guar gum, of zero-valent iron nanoparticles in the Journal of Colloid and Interface Science 324(1-2): 71presence of guar gum 79 (2008) B. B. Vardhanabhuti, E. A. Foegeding: Effects of Effects of dextran sulfate, NaCl, and initial dextran sulfate, NaCl, and initial protein concentration protein concentration on thermal stability on thermal stability of beta-lactoglobulin and alphalactalbumin at neutral pH, Food Hydrocolloids 22(5): of beta-lactoglobulin and alphalactalbumin at neutral pH 752-762 (2008) K. E. D. Coan, B. K. Shoichet: Stoichiometry and Physical Chemistry of Promiscuous Aggregate-Based Stoichiometry and Physical Chemistry of Inhibitors, Journal of the American Chemical Society Promiscuous Aggregate-Based Inhibitors 130(29): 9606-9612 (2008) D. A. Bateman, J. McLaurin, A. Chakrabartty: Requirement of aggregation propensity of Requirement of aggregation propensity of Alzheimer Alzheimer amyloid peptides for neuronal amyloid peptides for neuronal cell surface binding, BMC Neuroscience 8(29): 1-13 (2007) cell surface binding E. N. Salgado, J. Faraone-Mennella, F. A. Tezcan: Controlling Protein-Protein Interactions through Metal Controlling Protein-Protein Interactions Coordination: Assembly of a 16-Helix Bundle Protein, through Metal Coordination: Assembly of Journal of the American Chemical Society 129(44): a 16-Helix Bundle Protein 13374-13375 (2007) E. N. Salgado, J. Faraone-Mennella, F. A. Tezcan: Supplemental information for: Controlling Supplemental information for: Controlling ProteinProtein-Protein Interactions through Metal Protein Interactions through Metal Coordination: Assembly of a 16-Helix Bundle Protein, Journal of the Coordination: Assembly of a 16-Helix Bundle Protein American Chemical Society 129(44): S1-S8 (2007) H. L. Bagger, L. H. Øgendal, P. Westh: Solute effects on the irreversible aggregation of serum albumin, Solute effects on the irreversible aggregation of serum albumin Biophysical Chemistry 130(1-2): 17-25 (2007) Page 20 of 46 AAPS Focus Group Aggregation and Biological Consequences Literature Collection Protein In vitro In vitro In vitro In vitro Ver Meer Effect of Mesoporosity on Thermal and Mechanical Properties of Polystyrene/Silica Composites Hepatitis B Antigen Li Characterization of the large size aggregation of Hepatitis B virus surface antigen (HBsAg) formed in ultrafiltration process Acylated chitosan Hu Self-aggregation and antibacterial activity of N-acylated chitosan Bateman Requirement of aggregation propensity of Alzheimer amyloid peptides for neuronal cell surface binding Ueda Solubility-insolubility interconversion of sophoragrin, a mannose/glucose-specific lectin in sophora japonica (Japanese pagoda tree) bark, regulated by the sugar-specific interaction Meyer Protein purification by fusion with an environmentally responsive elastin-like polypeptide: effect of polypeptide length on the purification of thioredoxin prion protein Polystyrene/Silica Protein In vitro In vitro Erlich Complement Protein C1q Forms A Complex With Cytotoxic Prion Protein Oligomers adenovirus -based vaccine In vitro In vitro Renteria Development of a nasal adenovirusbased vaccine: Effect of concentration and formulation on adenovirus stability and infectious titer during actuation from two delivery devices Peptide Protein Protein Amyloid Sophoragrin Thioreduxin Page 21 of 46 Version 30 July 2010 S. S. Renteria, C. C. Clemens, M. A. Croyle: Development of a nasal adenovirus-based vaccine: Effect of concentration and formulation on adenovirus stability and infectious titer during actuation from two delivery devices, Vaccine 28(9): 2137-2148 (2010) P. Erlich, C. Dumestre-Perard, W. L. Ling, C. Lemaire-Vieille, G. Schoehn, G. J. Arlaud, N. M. Thielens, J. Gagnon, J.-Y. Cesbron: Complement Protein C1q Forms A Complex With Cytotoxic Prion Protein Oligomers, The Journal of Biological Chemistry 285: 19267-19276 (2010) M. A. Ver Meer, B. Narasimhan, B. H. Shanks, S. K. Mallapragada: Effect of Mesoporosity on Thermal and Mechanical Properties of Polystyrene/Silica Composites, Applied Materials & Interfaces 2(1): 4147 Y. Li, J. Bi, W. Zhou, Y. Huang, L. Sun, A.-P. Zeng, G. Ma, Z. Su: Characterization of the large size aggregation of Hepatitis B virus surface antigen (HBsAg) formed in ultrafiltration process, Process Biochemistry 42(3): 315-319 (2007) Y. Hu, Y. Du, J. Yang, Y. Tang, J. Li, X. Wang: Selfaggregation and antibacterial activity of N-acylated chitosan, Polymer 48(11): 3098-3106 (2007) D. A. Bateman, J. McLaurin, A. Chakrabartty: Requirement of aggregation propensity of Alzheimer amyloid peptides for neuronal cell surface binding, BMC Neuroscience 8(29): 1-13 (2007) H. Ueda, H. Fukushima, Y. Hatanaka, H. Ogawa: Solubility-insolubility interconversion of sophoragrin, a mannose/glucose-specific lectin in sophora japonica (Japanese pagoda tree) bark, regulated by the sugarspecific interaction, Biochemical Journal 382: 821-829 (2004) D. E. Meyer, K. Trabbic-Carlson, A. Chilkoti: Protein purification by fusion with an environmentally responsive elastin-like polypeptide: effect of polypeptide length on the purification of thioredoxinvol, Biotechnology Progress 17(4): 720728 (2001) AAPS Focus Group Aggregation and Biological Consequences Literature Collection 3.4 Immunogenicity observation - acute and/or sporadic N/A 3.5 Immunogenicity observation - chronic and/or general N/A 3.6 Immunogenicity assays N/A Page 22 of 46 Version 30 July 2010 AAPS Focus Group Aggregation and Biological Consequences Literature Collection Version 30 July 2010 4 Aggregate/Particle detection/characterization Data Source Substance Class In vitro Protein Further substance classification / Substance name Capelle In vitro In vitro Corresponding author / Group head El Seoud Calsequestrin Shadle in vitro Lignin Gidh In vitro Lignin Gidh In vitro Lignin Gidh In vitro No experimental data Protein Protein Ye Liu Title Full citation M. A. H. Capelle, R. Gurny, T. Arvinte: High throughput High throughput screening of protein screening of protein formulation stability: practical considerations, European Journal of Pharmaceutics and formulation stability: practical considerations Biopharmaceutics 65(2): 131-148 (2007) O. A. El Seoud, P. A. R. Pires, T. Abdel-Moghny, E. L. Bastos: Synthesis and micellar properties of surfaceSynthesis and micellar properties of active ionic liquids: 1-Alkyl-3-methylimidazolium surface-active ionic liquids: 1-Alkyl- chlorides, Journal of colloid and Interface Science 313(1): 3-methylimidazolium chlorides 296-304 (2007) S. E. Shadle, R. Rostock, L. Bonfrisco, M. E. Schimpf: Study of Calsequestrin Aggregation by Flow Field-Flow Study of Calsequestrin Aggregation Fractionation with Light Scattering Detection, Journal of by Flow Field-Flow Fractionation Liquid Chromatography & Related Technologies 30 with Light Scattering Detection (9&10): 1513-1523 (2007) A. V. Gidh, S. R. Decker, C. H. See, M. E. Himmel, C. W. Williford: Characterization of lignin using multi-angle laser Characterization of lignin using multi-angle laser light scattering and light scattering and atomic force microscopy, Analytica Chimica Acta 555(2): 250-258 (2006) atomic force microscopy A. V. Gidh, S. R. Decker, T. B. Vinzant, M. E. Himmel, C. W. Williford: Fungal-induced redistribution of kraft lignin Fungal-induced redistribution of kraft molecular weight by multi-angle laser light scattering, lignin molecular weight by multiChemical Engineering Communications 193: 1546-1561 angle laser light scattering (2006) A. V. Gidh, S. R. Decker, T. B. Vinzant, M. E. Himmel, C. Williford: Determination of lignin by size exclusion Determination of lignin by size exclusion chromatography using chromatography using multi angle laser light scattering, Journal of Chromatography A 1114(1): 102-110 (2006) multi angle laser light scattering Simultaneous determination of H. Ye: Simultaneous determination of protein protein aggregation, degradation, and absolute molecular weight by aggregation, degradation, and absolute molecular weight size exclusion chromatographyby size exclusion chromatography-multiangle laser light multiangle laser light scattering scattering, Analytical Biochemistry 356: 76-85 (2006) A critical review of analytical J. Liu, J. D. Andya, S. J. Shire: A critical review of ultracentrifugation and field flow analytical ultracentrifugation and field flow fractionation fractionation methods for measuring methods for measuring protein aggregation, The AAPS protein aggregation Journal 8(3): E580-E589 (2006) Page 23 of 46 AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro Antibody Moll In vitro Whittaker In vitro terbenzimidazoles Khan In vitro Peptid Novispirin G-10 Wimmer In vitro Protein antifreeze glycoprotein Bouvet In vitro Protein de Marco In vitro Protein Schimmele In vitro Yao In vitro Sodium dodecylsulfate In vitro DNA Thévenot Version 30 July 2010 J. R. Moll, V. Miranda, Y.-M. Li, L. Bergerud, T. M. Spitznagel, M. P. Byrne: Characterization of Purified Antibody Dimers (2006) M. R. Whittaker, M. J. Monteiro: Synthesis and aggregation behavior of four-arm star amphiphilic block copolymers in water, Langmuir 22(23):9746-9752 (2006) Q. A. Khan, C. M. Barbieri, A. R. Srinivasan, Y.-H. Wang, E. J. LaVoie, D. S. Pilch: Drug self-association modulates Drug self-association modulates the the cellular bioavailability of DNA minor groove-directed cellular bioavailability of DNA minor terbenzimidazoles, Journal of Medicinal Chemistry groove-directed terbenzimidazoles 49(17):5245-5251 (2006) R. Wimmer, K. K. Andersen, B. Vad, M. Davidsen, S. Mølgaard, L. W. Nesgaard, H. H. Kristensen, D. E. Versatile interactions of the Otzen: Versatile interactions of the antimicrobial peptide antimicrobial peptide novispirin with novispirin with detergents and lipids, Biochemistry 45(2): detergents and lipids 481-497 (2006) V. R. Bouvet, G. R. Lorello, R. N. Ben: Aggregation of Aggregation of antifreeze antifreeze glycoprotein fraction 8 and its effect on glycoprotein fraction 8 and its effect antifreeze activity, Biomacromolecules 7(2): 565on antifreeze activity 71(2006) Native folding of aggregation-prone A. de Marco, L. Vigh, S. Diamant, P. Goloubinoff: Native recombinant proteins in escherichia folding of aggregation-prone recombinant proteins in coli by osmolytes, plasmid- or escherichia coli by osmolytes, plasmid- or benzyl alcoholbenzyl alcohol-overexpressed overexpressed molecular chaperones, Cell Stress & molecular chaperones Chaperones 10(4): 329–339 (2005) B. Schimmele, N. Grafe, A. Pluckthun: Ribosome display of mammalian receptor domains, Protein Engineering, Ribosome display of mammalian Design & Selection 18(6): 285-294 (2005) receptor domains B. Yao, B. Collins, M. Chen: Light scattering to detect Light scattering to detect compound compound aggregation in screening assays, Drug Plus International (2005) aggregation in screening assays C. Thévenot, B. Grassl, G. Bastiat, W. Binana: Aggregation number and critical Aggregation number and critical micellar concentration of surfactant determined by time-dependent static light micellar concentration of surfactant determined by time-dependent static scattering (TDSLS) and conductivity, Colloids and Surfaces A: Physicochemical Engineering Aspects 252: light scattering (TDSLS) and 105-111 (2005) conductivity E. Tan, J. Wong, D. Nguyen, Y. Zhang, B. Erwin, L. K. Van Ness, S. M. Baker, D. J. Galas, A. Niemz: Isothermal Isothermal DNA amplification DNA amplification coupled with DNA nanosphere-based coupled with DNA nanospherecolorimetric detection, Analytical Chemistry 77(24): 7984based colorimetric detection 7992 (2005) Characterization of Purified Antibody Dimers Synthesis and aggregation behavior of four-arm star amphiphilic block copolymers in water Page 24 of 46 AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro Silver- colloid Bengter zFP538 Zubova In vitro Protein In vitro Protein Shen In vitro Protein Jancarik In vitro red blood cells In vitro Yun In vitro In vitro Armstrong Peptid liposomes Zhang parathyroid hormone Kamberi New light on Ag-colloid preparation for surface-enhanced FT-Raman spectroscopy: the role of aggregation Version 30 July 2010 H. Bengter, C. Tengroth, S. P. Jacobsson: New light on Ag-colloid preparation for surface-enhanced FT-Raman spectroscopy: the role of aggregation, Journal of Raman Spectroscopy 36: 1015-1022 (2005) N. N. Zubova, V. A. Korolenko, A. A. Astafyev, A. N. Petrukhin, L. M. Vinokurov, O. M. Sarkisov, A. P. Brightness of yellow fluorescent Savitsky: Brightness of yellow fluorescent protein from protein from coral (zFP538) coral (zFP538) depends on aggregation, Biochemistry depends on aggregation 44(10): 3982-3993 (2005) W. Shen, R. G. H. Lammertink, J. K. Sakata, J. A. Kornfield, D. A. Tirrell: Assembly of an artificial protein Assembly of an artificial protein hydrogel through leucine zipper aggregation and disulfide hydrogel through leucine zipper bond formation, Macromolecules 38(9): 3909-3916 aggregation and disulfide bond (2005) formation J. Jancarik, R. Pufan, C. Hong, S.-H. Kim, R. Kim: Optimum solubility (OS) screening: an efficient method to Optimum solubility (OS) screening: optimize buffer conditions for homogeneity and an efficient method to optimize crystallization of proteins, Acta Crystallographica 60(Pt buffer conditions for homogeneity 9): 1670-1673 (2004) and crystallization of proteins J. K. Armstrong, R. B. Wenby, H. J. Meiselman, T. C. Fisher: The hydrodynamic radii of macromolecules and The hydrodynamic radii of macromolecules and their effect on their effect on red blood cell aggregation, Biophysical Journal 87 (6): 4259-4270 (2004) red blood cell aggregation J. Yun, R. Faust, L. Sz. Szilágyi, S. Kéki, M. Zsuga: Effect of architecture on the micellar Effect of architecture on the micellar properties of amphiphilic block copolymers: comparison of AB linear properties of amphiphilic block copolymers: comparison of AB diblock, A2B2, A3B3, and (AB)3 star block copolymers, Journal of Macromolecular Science: Part A-Pure and linear diblock, A2B2, A3B3, and (AB)3 star block copolymers Applied Chemistry 41(6): 613-627 (2004) L. Zhang, T. Peng, S.-X. Cheng, R.-X Zhuo: Destabilization of liposomes by Destabilization of liposomes by uncharged hydrophilic and amphiphilic polymers, Journal of Physical Chemistry uncharged hydrophilic and amphiphilic polymers B 108(23): 7763-7770 (2004) Analysis of non-covalent M. Kamberi, P. Chung, R. DeVas, L. Li, Z. Li, X. Ma aggregation of synthetic hPTH (1(Sharon), S. Fields, C. M. Riley: Analysis of non-covalent 34) by size-exclusion aggregation of synthetic hPTH (1-34) by size-exclusion chromatography and the importance chromatography and the importance of suppression of of suppression of non-specific non-specific interactions for a precise quantitation, interactions for a precise Journal of Chromatography B, Analytical technologies in quantitation the biomedical and life sciences 810(1): 151-155 (2004) Page 25 of 46 AAPS Focus Group Aggregation and Biological Consequences Literature Collection superoxide dismutase-1 Ray In vitro Copolymers Annenkov In vitro ether-linked fluorocarbon Huang lysozyme Gu Amylopectin Olsson Myosin López-Díaz Copolymer Yun In vitro In vitro Protein Protein In vitro In vitro Protein In vitro In vitro In vitro Protein Rhazi beta-cyclodextrin, Nacylurea Soltés An intersubunit disulfide bond prevents in vitro aggregation of a superoxide dismutase-1 mutant linked to familial amytrophic lateral sclerosis Version 30 July 2010 S. S. Ray, R. J. Nowak, K. Strokovich, R. H. Brown, Jr., T. Walz, P. T. Lansbury, Jr.: An intersubunit disulfide bond prevents in vitro aggregation of a superoxide dismutase-1 mutant linked to familial amytrophic lateral sclerosis, Biochemistry 43(17): 4899-4905 (2004) V. V. Annenkov, E. N. Danilovtseva, H. Tenhu, V. Aseyev, S.-P. Hirvonen, A. I. Mikhaleva: Copolymers of Copolymers of 1-vinylimidazole and 1-vinylimidazole and (meth)acrylic acid: Synthesis and (meth)acrylic acid: Synthesis and polyelectrolyte properties, European Polymer Journal polyelectrolyte properties 40(6): 1027-1032 (2004) W. Huang, C. Jin, D. K. Derzon, T. A. Huber, J. A. Last, P. P. Provencio, A. S. Gopalan, M. Dugger, D. Y. Sasaki: Synthesis of ether-linked fluorocarbon surfactants and their Synthesis of ether-linked fluorocarbon surfactants and their aggregational properties in organic solvents, Journal aggregational properties in organic solvents of Colloid and Interface Science 272(2): 457-464 (2004) Z. Gu, X. Zhu, S. Ni, Z. Su, H.-M. Zhou: Conformational changes of lysozyme refolding intermediates and Conformational changes of lysozyme refolding intermediates implications for aggregation and renaturation, The and implications for aggregation and International Journal of Biochemistry & Cell Biology renaturation 36(5): 795-805 (2004) C. Olsson, T. Frigård, R. Andersson, A.-M. Hermansson: Effects of amylopectin structure and Effects of amylopectin structure and molecular weight on molecular weight on microstructural microstructural and rheological properties of mixed betaand rheological properties of mixed lactoglobulin gels, Biomacromolecules 4(5): 1400-1409 (2003) beta-lactoglobulin gels J. A. López-Díaz, A. Rodríguez-Romero, A. HernándezSantoyo, R. R. Sotelo-Mundo, A. M. Calderón de la Effects of Soy Glycinin Addition on Barca: Effects of Soy Glycinin Addition on the the Conformation and Gel Strength Conformation and Gel Strength of Two Pork Myosin of Two Pork Myosin Types Types, Journal of Food Science 68(9): 2724-2729 (2003) Effect of architecture on the micellar J. Yun, R. Faust, L. Sz. Szilagyi, S. Keki, M. Zsuga: properties of amphiphilic block Effect of architecture on the micellar properties of copolymers: comparison of AB amphiphilic block copolymers: comparison of AB linear linear diblock, A1A2B, and A2B diblock, A1A2B, and A2B heteroarm star block heteroarm star block copolymers copolymers, Macromolecules 36(5): 1717-1723 (2003) Sulfhydryl-disulfide changes in storage proteins of developing L. Rhazi, R. Cazalis, T. Aussenac: Sulfhydryl-disulfide wheat grain: influence on the SDSchanges in storage proteins of developing wheat grain: unextractable glutenin polymer influence on the SDS-unextractable glutenin polymer formation formation, Journal of Cereal Science 38(3): 3-13 (2003) Molecular characterization of two L. Soltés, R. Mendichi: Molecular characterization of two host–guest associating hyaluronan host–guest associating hyaluronan derivatives, derivatives Biomedical Chromatography 17(6): 376-384 2003) Page 26 of 46 AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro In vitro Protein In vitro In vitro, In vivo animal Polysaccarides Simon Tau Protein Yao copolymers Waddon Protein Thoma In vitro In vitro amylopectin Blennow In vitro cyclic amides Pethica In vitro Pullulan Duval Discosomar fluorescent protein Mizuno In vitro Protein Amphiphilic polysaccharides. Evidence for a competition between intra and intermolecular associations in dilute system Version 30 July 2010 S. Simon, J.Y. Dugast, D. Le Cerf, L. Picton, G. Muller: Amphiphilic polysaccharides. Evidence for a competition between intra and intermolecular associations in dilute system, Polymer 44(26): 7917-7924 (2003) T.-M. Yao, K. Tomoo, T. Ishida, H. Hasegawa, M. Sasaki, T. Taniguchi: Aggregation Analysis of the Microtubule Aggregation Analysis of the Binding Domain in Tau Protein by Spectroscopic Microtubule Binding Domain in Tau Methods, The Journal of Biochemistry 134(1): 91-99 Protein by Spectroscopic Methods (2003) A. J. Waddon, L. Zheng, R. J. Farris, E. B. Coughlin: Nanostructured polyethylene-POSS Nanostructured polyethylene-POSS copolymers: control copolymers: control of crystallization of crystallization and aggregation, Nano Letters 2(10): and aggregation 1149-1155 (2002) G. Thoma, A.G. Katopodis, N. Voelcker, R.O. Duthaler, M.B. Streiff: Novel Glycodendrimers Self-Assemble to Novel Glycodendrimers SelfAssemble to Nanoparticles which Nanoparticles which Function as Polyvalent Ligands In Vitro and In Vivo, Angewandte Chemie International Function as Polyvalent Ligands In Vitro and In Vivo Edition 41(17): 3195-3198 (2002) Sugar-based surfactants: adsorption R. C. Bazito, O. A. El Seoud: Sugar-based surfactants: and micelle formation of sodium adsorption and micelle formation of sodium methyl 2methyl 2-acylamido-2-deoxy-6-Oacylamido-2-deoxy-6-O-sulfo-D-glucopyranosides, sulfo-D-glucopyranosides Langmuir 18(11): 4362-4366 (2002) Amylopectin aggregation as a A. Blennow, A. M. Bay-Smidt, R. Bauer: Amylopectin function of starch phophate content aggregation as a function of starch phophate content studied by size exclusion studied by size exclusion chromatography and on-line chromatography and on-line refractive index and light scattering, International Journal refractive index and light scattering of Biological Macromolecules 28(5): 409-420 (2001) Surface and colloidal properties of B. A. Pethica, L. Senak, Z. Zhu, A. Lou: Surface and cyclic amides. 5. N-cyclohexyl-2colloidal properties of cyclic amides. 5. N-cyclohexyl-2pyrrolidone-water mixtures pyrrolidone-water mixtures aggregation in solution and aggregation in solution and adsorption at the air-solution interface, Colloids and adsorption at the air-solution Surfaces A: Physiochemical and Engineering Aspects interface 186(1-2): 113-122 (2001) C. Duval, D. Le Cerf, L. Picton, G. Muller: Aggregation of amphiphilic pullulan derivatives evidenced by on-line flow Aggregation of amphiphilic pullulan derivatives evidenced by on-line field flow fractionation/multi-angle laser light scattering, Journal of chromatography. B, Biomedical sciences and flow field flow fractionation/multiangle laser light scattering applications 753(1): 115-122 (2001) Red fluorescent protein from H. Mizuno, A. Sawano, P. Eli, H. Hama, A. Miyawaki: Discosoma as a fusion tag and a Red fluorescent protein from Discosoma as a fusion tag partner for fluorescence resonance and a partner for fluorescence resonance energy energy transfer transfer, Biochemistry 40(8): 2502-2510 (2001) Page 27 of 46 AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro humic acid Manning In vitro Peptid acylated peptide Clodfelter In vitro Protein interferon-γ Kendrick In vitro antineoplastic glucan (PS1A1) Farrugia In vitro dioctyl-polyfluorene Grell apoprotein A-l Bolaños-García titania nanoparticles Moran In vitro In vitro Protein In vitro Wyatt In vitro Wyatt Version 30 July 2010 T. J. Manning, T. Bennett, D. Milton: Aggregation studies of humic acid using multiangle laser light scattering, The Science of the Total Environment 257(2-3): 171-176 (2000) D. K. Clodfelter, M. A. Nussbaum, J. Reilly: Comparison Comparison of free solution capillary of free solution capillary electrophoresis and size electrophoresis and size exclusion exclusion chromatography for quantitating non-covalent aggregation of an acylated peptide, Journal of chromatography for quantitating non-covalent aggregation of an Pharmaceutical and Biomedical Analysis 19(5): 763-775 (1999) acylated peptide B. S. Kendrick, J. F. Carpenter, J. L. Cleland, T. W. Randolph: A transient expansion of the native state precedes aggregation of recombinant human interferonγ, Proceedings of the National Academy of Sciences of A transient expansion of the native state precedes aggregation of the United States of America 95(24): 14142–14146 (1998) recombinant human interferon-γ Comparative measurement of the I. V. Farrugia, E. J. Dadey, K. Ashline, M. J. Groves: molecular weight of an Comparative measurement of the molecular weight of an antineoplastic glucan from BCG antineoplastic glucan from BCG vaccine, The Journal of vaccine Pharmacy and Pharmacology 50(11): 1205-1211 (1998) Chain geometry, solution M. Grell, D. D. C. Bradley, X. Long, T. Chamberlain, M. aggregation and enhanced Inbasekaran, E. P. Woo, M. Soliman: Chain geometry, dichroism in the liquid-crystalline solution aggregation and enhanced dichroism in the conjugated polymer poly(9,9liquid-crystalline conjugated polymer poly(9,9dioctylfluorene) dioctylfluorene), Acta Polymerica 49(8): 439-444 (1998) V. M. Bolaños-García, J. Mas-Oliva, M. Soriano-García, A. Moreno: Precrystallization of human apoprotein A-I Precrystallization of human based on its aggregation behavior in solution studied by apoprotein A-I based on its dynamic light scattering, Journal of Molecular Structure aggregation behavior in solution 440(1-3):1-8 (1998) studied by dynamic light scattering P. D. Moran, J. R. Bartlett, J. L. Woolfrey, G. A. Bowmaker, R. P. Cooney: Formation and gelation of Formation and gelation of titania nanoparticles from AOT reverse titania nanoparticles from AOT reverse micelles, Journal of Sol-Gel Science and Technology 8(1-3): 65-69 (1997) micelles Multiangle light scattering combined P. J. Wyatt: Multiangle light scattering combined with with HPLC -- LC GC back to the HPLC -- LC GC back to the basics, LCGC 15: 160-168 basics (1997) Multiangle light scattering: The basic P. J. Wyatt: Multiangle light scattering: The basic tool for tool for macromolecular macromolecular characterization, Instrumentation characterization Science & Technology 25(1): 1-18 (1997) Aggregation studies of humic acid using multiangle laser light scattering Page 28 of 46 AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro copolymers Khougaz In vitro Pectins Rinaudo In vitro poly (acrylamide) Ying human growth hormone DeFelippis In vitro κ- carrageenan Viebke In vitro polystyrene Zhong In vitro Protein In vitro Van Zanten In vitro cyclodextrin In vitro Salamone In vitro In vitro Petter Protein gemini pseudoglyceryl lipid membrane Bhattacharya Succinylated Gelatin Liu Aggregation and critical Micelle concentrations of polystyrene-bpoly(sodium acrylate) and polystyrene-b-poly(acrylic acid) Micelles in Organic Media Version 30 July 2010 K. Khougaz, X. F. Zhong, A. Eisenberg: Aggregation and critical Micelle concentrations of polystyrene-bpoly(sodium acrylate) and polystyrene-b-poly(acrylic acid) Micelles in Organic Media, Macromolecules, Macromolecules 29(11): 3937-3949 (1996) M. Rinaudo: Physicochemical properties of pectins in solution and gel states, Pectins and Pectinases 14: 21-34 Physicochemical properties of (1996) pectins in solution and gel states Laser light scattering of Q. Ying, G. Wu, B. Chu, R. Farinato, L. Jackson: Laser poly(acrylamide) in 1 M NaCl light scattering of poly(acrylamide) in 1 M NaCl aqueous aqueous Solution Solution, Macromolecules 29(13): 4646-4654 (1996) M. R. DeFelippis, M. A. Kilcomons, M. P. Lents, K. M. Youngman, H. A. Havel: Acid Stabilization of human Acid Stabilization of human growth hormone equilibrium folding growth hormone equilibrium folding intermediates, Biochimica et Biophysica acta BBA 1247(1):35-45 (1995) intermediates C. Viebke, L. Piculell, S. Nilsson: On the mechanism of gelation of helix forming biopolymers, Macromolecules 27 On the mechanism of gelation of helix forming biopolymers (15): 4160–4166 (1994) X. F. Zhong, A. Eisenberg: Aggregation and critical Aggregation and critical micellization micellization behavior of carboxylate-terminated behavior of carboxylate-terminated monochelic polystyrene, Macromolecules 27 (7): 1751– 1758 (1994) monochelic polystyrene J. M. Van Zanten, M. Elimelech: Determination of absolute coagulation rate constants by multiangle light Determination of absolute coagulation rate constants by scattering, Journal of Colloid and Interface Science 154(1):1-7(1992) multiangle light scattering R. C. Petter, J. S. Salek, C. T. Sikorski, G. Kumaravel, F.-T. Lin: Cooperative binding by aggregated mono-6Cooperative binding by aggregated (alkylamino)-β-cyclodextrins, Journal of the American mono-6-(alkylamino)-β-cyclodextrins Chemical Society 112(10): 3860–3868 (1990) J. C. Salamone, J. C., A. M. Thompson, C. H. Su, A. C. Watterson: Associated Polymers in solution, American Chemical Society Proc., Polym. Mat. Sci. Eng. 61: 518521(1988) Associated Polymers in solution Thermotropic and hydration studies S. Bhattacharya, A. Bajaj: Thermotropic and hydration of membranes formed from gemini studies of membranes formed from gemini pseudoglyceryl lipids possessing pseudoglyceryl lipids possessing polymethylene spacers, polymethylene spacers Langmuir 23(17): 8988-8994 (2007) Determination of Modification T. Liu, G.-F. Zhang, W.-B. Zhou, Z.-G. Su: Determination Degree of Succinylated Gelatin by of Modification Degree of Succinylated Gelatin by Size Size Exclusion Chromatography Exclusion Chromatography Coupled with Multi Angle Coupled with Multi Angle Laser Light Laser Light Scattering, Chinese Journal of Analytical Scattering Chemistry 35(1): 43-48 (2007) Page 29 of 46 AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro Protein In vitro Antibody IgG Hawe In vitro Protein Polyomavirus VP1 Lipin Lipopolysaccarid Sasaki Amyloid Beta Kotarek Methylcellulose Zhou Rapid and quantitative determination of critical micelle concentration by automatic continuous mixing and static light scattering Lipeo-sCT: A novel reversible lipidized salmon calcitonin derivative, its biophysical properties and hypocalcemic activity Characterization of High-MolecularWeight Nonnative Aggregates and Aggregation Kinetics by Size Exclusion Chromatography With Inline Multi-Angle Laser Light Scattering Online fluorescent dye detection method for the characterization of immunoglobulin G aggregation by size exclusion chromatography and asymmetrical flow field flow fractionation Quaternary size distribution of soluble aggregates of glutathione-Stransferase-purified viral protein as determined by asymmetrical flow field flow fractionation and dynamic light scattering Aggregation Behavior of an UltraPure Lipopolysaccharide that Stimulates TLR-4 Receptors Quartz crystal microbalance analysis of growth kinetics for aggregation intermediates of the amyloid-beta protein Microstructure and aggregation behavior of methylcelluloses prepared in NaOH/urea aqueous solutions Ishikawa The Rough Endoplasmic Reticulumresident FK506-binding Protein FKBP65 Is a Molecular Chaperone That Interacts with Collagens In vitro Paillet In vivo animal Peptid In vitro In vitro Protein In vitro In vitro Protein Lipeo- salmon calcitonin Cheng Li FKBP65 Page 30 of 46 Version 30 July 2010 S. Paillet, B. Grassl, J. Desbrieres: Rapid and quantitative determination of critical micelle concentration by automatic continuous mixing and static light scattering, Analytica Chimica Acta 636(2): 236-241 (2009) W. Cheng, L.-Y. Lim: Lipeo-sCT: A novel reversible lipidized salmon calcitonin derivative, its biophysical properties and hypocalcemic activity, European Journal of Pharmaceutical Sciences 37(2): 151-159 (2009) Y. Li, W. F. Weiss IV, C. J. Roberts: Characterization of High-Molecular-Weight Nonnative Aggregates and Aggregation Kinetics by Size Exclusion Chromatography With Inline Multi-Angle Laser Light Scattering, Journal of Pharmaceutical Science 98(11): 3997-4016 (2009) A. Hawe, W. Friess, M. Sutter, W. Jiskoot: Online fluorescent dye detection method for the characterization of immunoglobulin G aggregation by size exclusion chromatography and asymmetrical flow field flow fractionation, Analytical Biochemistry 378(2): 115-122 (2008) D. I. Lipin, L. H. L. Lua, A. P. J. Middelberg: Quaternary size distribution of soluble aggregates of glutathione-Stransferase-purified viral protein as determined by asymmetrical flow field flow fractionation and dynamic light scattering, Journal of Chromatography A 1190(1-2): 204-214 (2008) H. Sasaki, S. H. White: Aggregation Behavior of an UltraPure Lipopolysaccharide that Stimulates TLR-4 Receptors, Biophysical Journal 95(2): 986-993 (2008) J. A. Kotarek, K. C. Johnson, M. A. Moss: Quartz crystal microbalance analysis of growth kinetics for aggregation intermediates of the amyloid-beta protein, Analytical Biochemistry 378(1): 15-24 (2008) J. Zhou, Y. Xu, X. Wang, Y. Qin, L. Zhang: Microstructure and aggregation behavior of methylcelluloses prepared in NaOH/urea aqueous solutions, Carbohydrate Polymers 74(4): 901-906 (2008) Y. Ishikawa, J. Vranka, J. Wirz, K. Nagata, H. P. Bächinger: The Rough Endoplasmic Reticulum-resident FK506-binding Protein FKBP65 Is a Molecular Chaperone That Interacts with Collagens, The Journal of Biological Chemistry 283(46): 31584-31590 (2008) AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro alginic acid Christensen In vitro cycoldextrin Bartlett In vitro Borgstahl In vitro In vitro Protein In vitro Protein In vitro Protein In vivo animal Protein lignin Gidh Human Apolipoprotein Moreno 0 Fields, G Interferon gamma Krishnan, S. Interferon Alpha2b Hermeling Suzanne Version 30 July 2010 Comment on "Conformational changes and aggregation of alginic acid as determined by fluorescence correlation spectroscopy" B. E. Christensen, G. Skjåk-Bræk, O. Smidsrød: Comment on "Conformational changes and aggregation of alginic acid as determined by fluorescence correlation spectroscopy", Biomacromolecules 8(10): 3279 (2007) D. W. Bartlett, M. E. Davis: Physicochemical and biological characterization of targeted, nucleic acidPhysicochemical and biological characterization of targeted, nucleic containing nanoparticles, Bioconjugate Chemistry 18(2): 456-468 (2007) acid-containing nanoparticles G. E. O. Borgstahl: How to Use Dynamic Light Scattering to Improve the Likelihood of Growing Macromolecular How to Use Dynamic Light Scattering to Improve the Likelihood Crystals, Methods in molecular biology 363: 109-129 of Growing Macromolecular Crystals (2007) A. V. Gidh, S. R. Decker, C. H. See, M. E. Himmel, C. W. Characterization of lignin using Williford: Characterization of lignin using multi-angle laser multi-angle laser light scattering and light scattering and atomic force microscopy, Analytica atomic force microscopy Chimica Acta 555(2):250-258 (2006) A. Moreno, J. Mas-Oliva, M. Soriano-García, C. O. Salvador, V. M. Bolaños-García: Turbidity as a useful Turbidity as a useful optical optical parameter to predict protein crystallization by parameter to predict protein dynamic light scattering, Journal of Molecular Structure crystallization by dynamic light 519(1-3): 243-256 (2000) scattering Fields, G., Alonso, D., Stiger, D., Dill K.: Theory for the aggregation of proteins and copolymers. J. Phys. Chem. Theory for the aggregation of 96:3974-3981, 1992 proteins and copolymers Aggregation of recombinant human Krishnan, S. et al.: Aggregation of recombinant human interferon gamma: kinetics and interferon gamma: kinetics and structural transitions. J. structural transitions Pharm. Sci. 87: 1069-1076, 1998 Antibody response to aggregated HermelingS., Schellekens H., Maas C., Gebbink M. F. G., human interferon alpha2b in wildCrommelin D. J. A., Jiskoot W.: Antibody response to type and transgenic immune tolerant aggregated human interferon alpha2b in wild-type and mice depends on type and level of transgenic immune tolerant mice depends on type and aggregation level of aggregation, JPS 95: 1084-1096 (2006) 4.1 Aggregate/Particle and molecular structure Data Source Substance Class In vitro Protein Further substance classification / Substance name Corresponding author / Group head Shen Title Structure and mechanical properties of artificial protein hydrogels assembled through aggregation of leucine zipper peptide domains Page 31 of 46 Full citation W. Shen, J. A. Kornfield, D. A. Tirrell: Structure and mechanical properties of artificial protein hydrogels assembled through aggregation of leucine zipper peptide domains, Soft Matter 3: 99-107 (2007) AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro In vitro Protein Protein In vitro alpha-synuclein alpha-synuclein Chitosan In vitro Dusa Characterization of oligomers during alphasynuclein aggregation using intrinsic tryptophan fluorescence Kaylor Characterization of oligomeric intermediates in alpha-synuclein fibrillation: FRET studies of Y125W/Y133F/Y136F alpha-synuclein Chen Effect of the Degree of Deacetylation and the Substitution of Carboxymethyl Chitosan on Its Aggregation Behavior Mozumder Influence of hydrophobe content and salt concentration on dilute solution behaviour of hydrophobically modified ionic polymers from diallylammonium salts/sulfur dioxide cyclocopolymerization: light scattering and fluorescence spectroscopy In vitro Protein β2-microglobulin Heegaard, Unfolding, aggregation, and seeded amyloid formation of lysine-58-cleaved β2microglobulin In vitro Protein fibrinogen Tsurupa Do the isolated fibrinogen alphaC-domains form ordered oligomers? Kashlan A comprehensive model for the allosteric regulation of mammalian ribonucleotide reductase. Functional consequences of ATP- and dATP-induced oligomerization of the large subunit Riley Physicochemical evaluation of nanoparticles assembled from poly(lactic acid)poly(ethylene glycol) (PLA-PEG) block copolymers as drug delivery vehicles In vitro In vitro Protein ribonucleotide reductase Copolymers Page 32 of 46 Version 30 July 2010 A. Dusa, J. Kaylor, S. Edridge, N. Bodner, D.-P. Hong, A. L. Fink: Characterization of oligomers during alphasynuclein aggregation using intrinsic tryptophan fluorescence, Biochemistry 45(8): 2752-2760 (2006) J. Kaylor, N. Bodner, S. Edridge, G. Yamin, D.-P. Hong, A. L. Fink: Characterization of oligomeric intermediates in alpha-synuclein fibrillation: FRET studies of Y125W/Y133F/Y136F alpha-synuclein, The Journal of Molecular Biology 353: 357-372 (2005) L. Chen, Y. Du, Z. Tian, L. Sun: Effect of the Degree of Deacetylation and the Substitution of Carboxymethyl Chitosan on Its Aggregation Behavior, Journal of Polymer Science: Part B: Polymer Physics, Journal of Polymer Science: Part B: Polymer Physics 43(3): 296-305 (2005) M. S. Mozumder, R. S. Alnaizy, Yunusa Umar, Sk. Asrof Ali, B. F. Abu-Sharkh: Influence of hydrophobe content and salt concentration on dilute solution behaviour of hydrophobically modified ionic polymers from diallylammonium salts/sulfur dioxide cyclocopolymerization: light scattering and fluorescence spectroscopy, European Polymer Journal 41(10): 22242231 (2005) N. H. H. Heegaard, T. J. D. Jørgensen, N. Rozlosnik, D. B. Corlin, J. S. Pedersen, A. G. Tempesta, P. Roepstorff, R. Bauer, M. H. Nissen: Unfolding, aggregation, and seeded amyloid formation of lysine-58-cleaved β2microglobulin, Biochemistry 44: 4397-4407 (2005) G. Tsurupa, Y. Veklich, R. Hantgan, A. M. Belkin, J. W. Weisel, L. Medved: Do the isolated fibrinogen alphaCdomains form ordered oligomers?Biophysical Chemistry 112(2-3): 257-266 (2004) O. B. Kashlan, C. P. Scott, J. D. Lear, B. S. Cooperman: A comprehensive model for the allosteric regulation of mammalian ribonucleotide reductase. Functional consequences of ATP- and dATP-induced oligomerization of the large subunit, Biochemistry 41(2): 462-474 (2002) T. Riley, S. Stolnik, C. R. Heald, C. D. Xiong, M. C. Garnett, L. Illum, S. S. Davis: Physicochemical evaluation of nanoparticles assembled from poly(lactic acid)poly(ethylene glycol) (PLA-PEG) block copolymers as drug delivery vehicles, Langmuir 17(11): 3168–3174 (2001) AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro surfactants Okano In vitro Protein CoA transferase Kay In vitro Protein RANTES Skelton In vitro polystyrene Zhong in vitro ProteinPolysaccharide Complex Tao In vitro copolymers Guan In vitro Peptid In vitro Peptide Amyloid Abeta (142) Rambaldi In vitro, In vivo animal Peptid Salmon calcitonin Cheng In vitro Sastry Wang Fluorescence and light-scattering studies of the aggregation of cationic surfactants in aqueous solution: effects of headgroup structure Version 30 July 2010 L. T. Okano, F. H. Quina, O. A. El Seoud: Fluorescence and light-scattering studies of the aggregation of cationic surfactants in aqueous solution: effects of headgroup structure, Langmuir 16(7): 3119–3123 (2000) J. -C. Rochet, K. Oikawa, L. D. Hicks, C. M. Kay, W. A. Bridger, W. T. Wolodko: Productive interactions between Productive interactions between the Two the Two domains of pig heart CoA transferase during domains of pig heart CoA transferase during folding and assembly, Biochemistry 36(29): 8807-8820 folding and assembly (1997) N. J. Skelton, F. Aspiras, J. Ogez, T. J. Schall: Proton Proton NMR Assignments and Solution NMR Assignments and Solution Conformation of Conformation of RANTES, a Chemokine of RANTES, a Chemokine of the C-C Type, Biochemistry the C-C Type 34(16): 5329-5342 (1995) X. F. Zhong, A. Eisenberg: Synthesis and characterization of 1,2-dicarboxyethyl-terminated Synthesis and characterization of 1,2dicarboxyethyl-terminated polystyrene polystyrene, Macromolecules 27 (18): 4914–4918 (1994) Y. Tao, F. Yan, L. Zhang: Fractionation and Characterization of a Protein-Polysaccharide Complex Fractionation and Characterization of a from Pleurotus tuberregium Sclerotia, Journal of Polymer Protein-Polysaccharide Complex from Science, Part B: Polymer Physics 45(18): 2546-2554 Pleurotus tuberregium Sclerotia (2007) Synthesis and Characterization of H. Guan, Z. Xie, P. Zhang, C. Deng, X. Chen, X. Jing: Biodegradable Amphiphilic Triblock Synthesis and Characterization of Biodegradable Copolymers Containing L-Glutamic Acid Amphiphilic Triblock Copolymers Containing L-Glutamic Units Acid Units, Biomacromolecules 6(4): 1954-1960 (2005) S. Sastry, N. Linderoth: Molecular Mechanisms of Molecular Mechanisms of Peptide Loading Peptide Loading by the Tumor Rejection Antigen/Heat by the Tumor Rejection Antigen/Heat Shock Shock Chaperone gp96 (GRP94), The Journal of Chaperone gp96 (GRP94) Biological Chemistry 274(17): 12023-12035 (1999) D. C. Rambaldi, A. Zattoni, P. Reschiglian, R. Colombo, E. De Lorenzi: In vitro amyloid Aß1-42 peptide In vitro amyloid Aß1-42 peptide aggregation aggregation monitoring by asymmetrical flow field-flow monitoring by asymmetrical flow field-flow fractionation with multi-angle light scattering detection, fractionation with multi-angle light scattering Analytica Bioanalytical Chemistry 394(8): 2145-2149 detection (2009) W. Cheng, L.-Y. Lim: Synthesis, Characterization and In Vivo Activity of Salmon Calcitonin Coconjugated With Synthesis, Characterization and In Vivo Activity of Salmon Calcitonin Coconjugated Lipid and Polyethylene Glycol, Journal of Pharmaceutical Science 98(4): 1438-1451 (2009) With Lipid and Polyethylene Glycol Amphiphilic Diblock Copolymers D. Wang, H. Ren, X. Wang, X. Wang: Amphiphilic Diblock Functionalized with Strong Push-Pull Azo Copolymers Functionalized with Strong Push-Pull Azo Chromophores: Synthesis and MultiChromophores: Synthesis and Multi-Morphological Morphological Aggregation Aggregation, Macromolecules 41 (23) : 9382-9388 (2008) Page 33 of 46 AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro Peptid Gordon Structural and functional properties of peptides based on the N-terminus of HIV-1 gp41 and the C-terminus of the amyloidbeta protein In vitro Protein STIM1, STIM2 Zheng Biophysical characterization of the EF-hand and SAM domain containing Ca2+ sensory region of STIM1 and STIM2 In vitro Protein DegP Krojer Structural basis for the regulated protease and chaperone function of DegP Takata Deamidation destabilizes and triggers aggregation of a lens protein, betaA3crystallin In vitro Protein betaA3-crystallin In vitro MTAC-BA-AM Cao Aggregation Behavior of Cationic Copolymer Methacryloxyethyl Trimethyl Ammonium Chloride-Butyl AcrylateAcrylamide in Aqueous Solution In vitro sodium alginat, curcubit[6] uril Huang Aggregation behavior of sodium alginate with cucurbit[6]uril in aqueous solution alphaB-crystallin Ecroyd Mimicking phosphorylation of alphaBcrystallin affects its chaperone activity Zanier Formation of well-defined soluble aggregates upon fusion to MBP is a generic property of E6 proteins from various human papillomavirus species In vitro In vitro Protein Protein E6 oncoprotein Page 34 of 46 Version 30 July 2010 L. M. Gordon, A. Nisthal, A. B. Lee, S. Eskandari, P. Ruchala, C.-L. Jung, A. J. Waring, P. W. Mobley: Structural and functional properties of peptides based on the N-terminus of HIV-1 gp41 and the C-terminus of the amyloid-beta protein, Biochimica et Biophysica Acta 1778(10): 2127-2137 (2008) L. Zheng, P. B. Stathopulos, G.-Y. Li, M. Ikura: Biophysical characterization of the EF-hand and SAM domain containing Ca2+ sensory region of STIM1 and STIM2, Biochemical and Biophysical Research Communications 369: 240-246 (2008) T. Krojer, J. Sawa, E. Schäfer, H. R. Saibil, M. Ehrmann, T. Clausen: Structural basis for the regulated protease and chaperone function of DegP, Nature 453: 885-890 (2008) T. Takata, J. T. Oxford, B. Demeler, K. J. Lampi: Deamidation destabilizes and triggers aggregation of a lens protein, betaA3-crystallin, Protein Science 17(9): 1565-1575 (2008) X. Cao, Y. Tan, G. Xu, D. Wu: Aggregation Behavior of Cationic Copolymer Methacryloxyethyl Trimethyl Ammonium Chloride-Butyl Acrylate-Acrylamide in Aqueous Solution, Journal of Dispersion Science and Technology 29(1): 70-76 (2008) X. Huang, Y. Tan, Q. Zhou, Y. Wang, Y. Che: Aggregation behavior of sodium alginate with cucurbit[6]uril in aqueous solution, Carbohydrate Polymers 74(3): 685-690 (2008) H. Ecroyd, S. Meehan, J. Horwitz, J.A. Aquilana, J.L.P. Benesche, C.V. Robinson, C.E. Macphee, J.A. Carver: Mimicking phosphorylation of alphaB-crystallin affects its chaperone activity, Biochemistry Journal 401: 129-141 (2007) K. Zanier, Y. Nominé, S. Charbonnier, C. Ruhlmann, P. Schultz, J. Schweizer, G. Travé: Formation of welldefined soluble aggregates upon fusion to MBP is a generic property of E6 proteins from various human papillomavirus species, Protein Expression and Purification 51(1): 59-70 (2007) AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro Protein superoxid dismutase Metal-free superoxide dismutase forms soluble oligomers under physiological conditions: A possible general mechanism for familial ALS Banci Version 30 July 2010 L. Banci, I. Bertini, A. Durazo, S. Girotto, E. Butler Gralla, M. Martinelli, J. Selverstone Valentine, M. Vieru, J.P. Whitelegge: Metal-free superoxide dismutase forms soluble oligomers under physiological conditions: A possible general mechanism for familial ALS, Biophysics PNAS 104 (27): 11263-11267 (2007) 4.2 Aggregate/Particle and long-term storage Data Source No experimental data Substance Class Further substance classification / Substance name Protein Corresponding author / Group head 0 Arakawa T. Title Factors affecting shortterm and long-term stabilities of proteins Full citation Arakawa T., Prestrelski S.J., Kenney W.C., Carpenter J.F.: Factors affecting short-term and long-term stabilities of proteins, Adv. Drug Deliv. Rev. 10: 1-28, 1993 4.3 Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t Substance Class Further substance classification / Substance name In vitro Protein bovine carbonic anhydrase Yan In vitro Protein Maltose-bindingprotein Huang In vitro Azobenzene Li In vitro Protein mouse prion protein Vendrely I In vitro Protein beta-lactoglobulin Data Source Corresponding author / Group head Zhu Title Fabrication of single carbonic anhydrase nanogel against denaturation and aggregation at high temperature Induced fit of passenger proteins fused to Archaea maltose binding proteins Formation of photoresponsive uniform colloidal spheres from an amphiphilic azobenzene-containing random copolymer Assembly of the full-length recombinant mouse prion protein I. Formation of soluble oligomers Studying Protein Aggregation by Programmed Flow Field-Flow Fractionation Using Ceramic Hollow Fibers Page 35 of 46 Full citation M. Yan, Z. Liu, D. Lu, Z. Liu: Fabrication of single carbonic anhydrase nanogel against denaturation and aggregation at high temperature, Biomacromolecules 8(2): 560-565 (2007) H. Huang, J. Liu, A. de Marco: Induced fit of passenger proteins fused to Archaea maltose binding proteins, Biochemical and Biophysical Research Communications 344(1): 25-29 (2006) Y. Li, Y. Deng, X. Tong, X. Wang: Formation of photoresponsive uniform colloidal spheres from an amphiphilic azobenzene-containing random copolymer, Macromolecules 39(3): 1108-1115 (2006) C. Vendrely, H. Valadié, L. Bednarova, L. Cardin, M. Pasdeloup, J. Cappadoro, J. Bednar, M. Rinaudo, M. Jamin: Assembly of the full-length recombinant mouse prion protein I. Formation of soluble oligomers, Biochimica et Biophysica Acta 1724(3): 355-366 (2005) R. Zhu, W. Frankema, Y. Huo, W. Th. Kok: Studying Protein Aggregation by Programmed Flow Field-Flow Fractionation Using Ceramic Hollow Fibers, Analytical Chemistry 77(14): 4581-4586 (2005) AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro Protein In vitro In vitro Protein In vitro In vitro In vitro Berg Cooperative binding of monodisperse anionic amphiphiles to the i-face: phospholipase A2-paradigm for interfacial binding poly(vinyl alcohol) Sho SEC-MALS characterization of aggregation behavior of poly(vinyl alcohol) in water actose whey Mleko copolymer Pispas phospholipase A2 Protein In vitro Fraunhofer Photon correlation spectroscopy investigations of proteins Aymmetrical Flow Field-Flow Fractionation in Pharmaceutical Analytics: Investigations in Aggregation Tendencies of Pharmaceutical Antibodies GonzálezGaitano The aggregation of cyclodextrins as studied by photon correlation spectroscopy Star-shaped poly(ethylene glycol)block-polyethylenimine copolymers enhance DNA condensation of low molecular weight polyethylenimines Gun’ko Antibody cyclodextrin Rheological properties of reduced lactose whey dispersions Micellization behavior of poly(butadiene-b-sodium methacrylate) copolymers in dilute aqueous media In vitro copolymers Petersen In vitro copolymers Sotiriou In vitro liposomes, latex Wang Micellization behavior of PS(PI)3 miktoarm star copolymers Aggregation rate measurements by zero-angle time-resolved multiangle laser light scattering de la Fuente Process-induced changes in whey proteins during the maufacture of whey protein concentrates In vitro Protein Whey Protein Page 36 of 46 Version 30 July 2010 O. G. Berg, B.-Z. Yu, C. Chang, K. A. Koehler, M. K. Jain: Cooperative binding of monodisperse anionic amphiphiles to the i-face: phospholipase A2-paradigm for interfacial binding, Biochemistry 43(25): 7999-8013 (2004) K. Sho, S. Kawaguchi: SEC-MALS characterization of aggregation behavior of poly(vinyl alcohol) in water, Japanese Journal of Polymer Science and Technology 60(6): 300-304 (2003) S. Mleko, P. Janas, T. Wang, J. A. Lucey: Rheological properties of reduced lactose whey dispersions, Int Journal of Dairy Technology 56(3): 157-161 (2003) S. Pispas, N. Hadjichristidis: Micellization behavior of poly(butadiene-b-sodium methacrylate) copolymers in dilute aqueous media, Macromolecules 36 (23): 8732-8737 (2003) V. M. Gun’ko, A. V. Klyueva, Y. N. Levchuk, R. Leboda: Photon correlation spectroscopy investigations of proteins, Advances in Colloid and Interface Science 105(1-3): 201328 Thesis: W. Fraunhofer: Aymmetrical Flow Field-Flow Fractionation in Pharmaceutical Analytics: Investigations in Aggregation Tendencies of Pharmaceutical Antibodies (2003) G. González-Gaitano, P. Rodríguez, J. R. Isasi, M. Fuentes, G. Tardajos, M. Sánchez: The aggregation of cyclodextrins as studied by photon correlation spectroscopy, Journal of Inclusion Phenomena and Macrocyclic Chemistry 44: 101105 (2002) H. Petersen, K. Kunath, A. L. Martin, S. Stolnik, C. J. Roberts, M. C. Davies, T. Kissel: Star-shaped poly(ethylene glycol)- block-polyethylenimine copolymers enhance DNA condensation of low molecular weight polyethylenimines, Biomacromolecules 3(5): 926-936 (2002) K. Sotiriou, A. Nannou, G. Velis, S. Pispas: Micellization behavior of PS(PI)3 miktoarm star copolymers, Macromolecules 35(10): 4106-4112 (2002) K. Wang, A. K. Singh, J. H. van Zanten: Aggregation rate measurements by zero-angle time-resolved multiangle laser light scattering, Langmuir 18(6): 2421-2425 (2002) M. A. de la Fuente, Y. Hemar, M. Tamehana, P. A. Munro, H. Singh: Process-induced changes in whey proteins during the maufacture of whey protein concentrates, International Dairy Journal 12(4): 361-369 (2002) AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro Protein In vitro Prefoldin Okochi Aeromonas Gum Zhang In vitro Protein dried egg white Handa In vitro Protein Apoferritin Petsev In vitro Clostridium difficile toxins Palace In vitro pectin Fishman In vitro Protein beta-lactoglobulin Ugolini In vitro Protein Apoferritin Petsev In vitro Erwinia gum In vitro polyvinyl chloride, dioxane Hong In vitro ionic dyestuff Inglés Version 30 July 2010 M. Okochi, T. Yoshida, T. Maruyama, Y. Kawarabayasi, H. Kikuchi, M. Yohda: Pyrococcus prefoldin stabilizes proteinPyrococcus prefoldin stabilizes protein- folding intermediates and transfers them to chaperonins for folding intermediates and transfers correct folding, Biochemical and Biophysical Research them to chaperonins for correct folding Communications 291(4): 769-774 (2002) X. Xu, L. Zhang, T. Norisuye: Molecular Weight and Molecular Weight and Aggregation of Aggregation of Aeromonas Gum Treated with Dimethyl Aeromonas Gum Treated with Dimethyl Sulfoxide in Aqueous Solution, Journal of Polymer Science: Sulfoxide in Aqueous Solution Part B: Polymer Physics 40(19): 2269-2276 (2002) A. Handa, K. Hayashi, H. Shidara, N. Kuroda: Correlation of Correlation of the protein structure and the protein structure and gelling properties in dried egg white products, Journal of Agricultural and Food Chemistry 49(8): gelling properties in dried egg white products 3957-3964 (2002) D. N. Petsev, B. R. Thomas, S.-T. Yau, D. Tsekova, C. Nanev, W. W. Wilson, P. G. Vekilov: TemperatureTemperature-independent solubility and independent solubility and interactions between apoferritin interactions between apoferritin monomers and dimers in solution, Journal of Crystal Growth monomers and dimers in solution 232(1-4): 21-29 (2001) Analysis of the physiochemical G. P. Palace, P. Lazari, K. Norton: Analysis of the interactions between Clostridium difficile physiochemical interactions between Clostridium difficile toxins and cholestyramine using liquid toxins and cholestyramine using liquid chromatography with chromatography with post-column post-column derivatization, Biochimica et Biophysica Acta derivatization 1546(1): 171-184 (2001) M. L. Fishman, H. K. Chau, F. Kolpak, J. Brady: Solvent effects on the molecular properties of pectins, Journal of Solvent effects on the molecular Agricultural and Food Chemistry 49(9): 4494-4501 (2001) properties of pectins R. Ugolini, L. Ragona, E. Silletti, F. Fogolari, R. W. Visschers, A. C. Alting, H. Molinari: Dimerization, stability Dimerization, stability and electrostatic and electrostatic properties of porcine beta-lactoglobulin, properties of porcine beta-lactoglobulin Euopean Journal of Biochemistry 268(16): 4477-4488 D. N. Petsev, B. R. Thomas, S.-T. Yasu, P. G. Vekilov: Interactions and aggregation of Interactions and aggregation of apoferritin molecules in apoferritin molecules in solution: effects solution: effects of added electrolytes, Biophysical Journal of added electrolytes 78(4): 2060-2069 (2000) L. Zhang, X. Xu, S. Pan: Effects of the thermal history and concentration on the aggregation of erwinia gum in aqueous Effects of the thermal history and solution, Journal of Polymer Science: Part B: Polymer concentration on the aggregation of erwinia gum in aqueous solution Physics 38(10): 1352 - 1358 (2000) Light scattering studies on aggregation P.-D. Hong, C.-M. Chou, J.-H. Chen: Light scattering studies behavior of polyvinyl chloride/dioxane on aggregation behavior of polyvinyl chloride/dioxane solutions solutions, Polymer 41(15): 5847-5854 (2000) Time-resolved recording of ionic S. E. Inglés, A. Katzenstein, W. Schlenker, K. Huber: Timedyestuff aggregation by static light resolved recording of ionic dyestuff aggregation by static scattering light scattering, Langmuir 16 (7): 3010–3018 (2000) Page 37 of 46 AAPS Focus Group Aggregation and Biological Consequences Literature Collection On the interchain associations in aqueous solutions of a succinoglycan polysaccharide In vitro Succinoglycan Boutebba In vitro Erwinia gum Zhang In vitro K-carrageenan Wittgren Rheological behavior of erwinia gum in aqueous solution Conformational change and aggregation of K-carrageenan studied by flow field-flow fractionation and multiangle light scattering Bossé Aggregation behaviour below the gelation threshold for metal-olefin coordination in diene polymers In vitro diene polymers in vitro block polyelectrolyte Khougaz Micellization in block polyelectrolyte solutions. 3. Static light scattering characterization In vitro poly(1,3-dioxolane) Benkhira Conformation of poly(1,3-dioxolane) in dilute and semidilute aqueous solutions In vitro heparin Mach Nature of the interaction of heparin with acidic fibroblast growth factor Hoppe Characterization of Purified Antibody Dimers A high throughput dimer screening assay for monoclonal antibodies using chemical cross-linking and microchip electrophoresis Characterization of seed nuclei in glucagon aggregation using light scattering methods and field-flow fractionation Kheirandish Shear and elongational flow behavior of acrylic thickener solutions Part I: Effect of intermolecular aggregation Demeule Characterization of protein aggregation: the case of a therapeutic immunoglobulin In vitro Antibody Moll In vitro Antibody Chen In vitro Peptid Glucagon In vitro In vitro Antibody IgA Page 38 of 46 Version 30 July 2010 A. Boutebba, M. Milas, M. Rinaudo: On the interchain associations in aqueous solutions of a succinoglycan polysaccharide, International Journal of Biological Macromolecules 24(4): 319-327 (1999) L. Zhang, M. Zhang, J. Chen, H. Iijima, H. Tsuchiya: Rheological behavior of erwinia gum in aqueous solution, Chinese Journal of Polymer Science 17(6): 557-561 (1999) B. Wittgren, J. Borgstron, L. Piculell, K. -G. Wahlund: Conformational change and aggregation of K-carrageenan studied by flow field-flow fractionation and multiangle light scattering, Biopolymers 45(1): 85-96 (1998) F. Bossé, P. Das, L. A. Belfiore: Aggregation behaviour below the gelation threshold for metal-olefin coordination in diene polymers, Polymer Gels and Networks 5(5): 387-413 (1997) K. Khougaz, I. Astafieva, A. Eisenberg: Micellization in block polyelectrolyte solutions. 3. Static light scattering characterization, Macromolecules 28 (21): 7135–7147 (1995) A. Benkhira, E. Franta, M. Rawiso, J. Fracois: Conformation of poly(1,3-dioxolane) in dilute and semidilute aqueous solutions, Macromolecules 27 (14): 3963–3972 (1994) H. Mach, D. B. Volkin, C. J. Burke, C. R. Middaugh: Nature of the interaction of heparin with acidic fibroblast growth factor, Biochemistry 32(20): 5480-5489 (1993) Poster: J. R. Moll, V. Miranda, Y.-M. Li, L. Bergerud, T. M. Spitznagel, M. P. Byrne: Characterization of Purified Antibody Dimers (2006) X. Chen, G. C. Flynn: A high throughput dimer screening assay for monoclonal antibodies using chemical crosslinking and microchip electrophoresis, Journal of Chromatography B 877(27): 3012-3018 (2009) C. C. Hoppe, L. T. Nguyen, L. E. Kirsch, J. M. Wiencek: Characterization of seed nuclei in glucagon aggregation using light scattering methods and field-flow fractionation, Journal of Biological Engineering 2:10 (2008) S. Kheirandish, I. Guybaidullin, W. Wohlleben, N. Willenbacher: Shear and elongational flow behavior of acrylic thickener solutions Part I: Effect of intermolecular aggregation, Rheologica Acta 47(9): 999-1013 (2008) B. Demeule, M. J. Lawrence, A. F. Drake, R. Gurny, T. Arvinte: Characterization of protein aggregation: the case of a therapeutic immunoglobulin, Biochimica et Biophysica Acta 1774(1): 146-153 (2007) AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro Antibody In vitro Gabrielson poly(1,3cyclohexadiene) Natori lumazine synthase Neumaier In vitro Protein In vitro Protein 0 Manning M.C Please select Protein 0 Chi E.Y. Version 30 July 2010 J. P. Gabrielson, M. L. Brader, A. H. Pekar, K. B. Mathis, G. Winter, J. F. Carpenter, T. W. Randolph: Quantitation of Aggregate Levels in a Recombinant Humanized Monoclonal Antibody Formulation by Size-Exclusion Chromatography, Asymmetrical Flow Field-Flow Fractionation, and Sedimentation Velocity, Journal of Pharmaceutical Sciences 96(2): 268-279 (2007) I. Natori, H. Sato: Aggregation of poly(1,3-cyclohexadiene): Aggregation of poly(1,3effects of molecular weight and polymer chain structure, Journal of Polymer Science Part B: Polymer Physics 44: cyclohexadiene): effects of molecular weight and polymer chain structure 1442-1452 (2006) Early stages of crystallization of Thesis: N. Neumaier: Early stages of crystallization of lumazine synthase from Bacillus subtilis lumazine synthase from Bacillus subtilis (2005) Manning M.C., Patel K., Borchhardt R.: Stability of Protein Pharmaceuticals. Pharm. Res. 6: 903-918 (1989) Stability of Protein Pharmaceuticals Chi E.Y., Krishnan S., Randolph T.W. and Carpenter J.F.: Physical Stability of Proteins in aqueous Solution: Physical Stability of Proteins in aqueous Mechanism and Driving Forces in Nonnative protein Solution: Mechanism and Driving aggregation, Pharm Research, Vol. 20, No. 9: 1325-1336 Forces in Nonnative protein aggregation (2003) Quantitation of Aggregate Levels in a Recombinant Humanized Monoclonal Antibody Formulation by Size-Exclusion Chromatography, Asymmetrical Flow Field-Flow Fractionation, and Sedimentation Velocity 4.4 Immunogenicity observation - acute and/or sporadic Data Source Substance Class In vitro Further substance classification / Substance name Corresponding author / Group head copolymers Petersen Title Synthesis, characterization, and biocompatibility of polyethyleniminegraft-poly(ethylene glycol) block copolymers Full citation H. Petersen, P. M. Fechner, D. Fischer, T. Kissel: Synthesis, characterization, and biocompatibility of polyethylenimine-graft-poly(ethylene glycol) block copolymers, Macromolecules 35(18): 6867-6874 (2002) 4.5 Immunogenicity observation - chronic and/or general N/A 4.6 Immunogenicity assays Data Source Substance Class Further substance classification / Substance name Corresponding author / Group head Title Full citation Page 39 of 46 AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vitro In vitro, In vivo animal Peptide In vitro, In vivo animal In vitro, In vivo animal Protein streptococcal pyrogenic exotoxins Proft Bacillus anthracis Joyce capsular polysaccharides Jin gp 41 Qiao Version 30 July 2010 T. Proft, V. L. Arcus, V. Handley, E. N. Baker, J. D. Fraser: Immunological and biochemical characterization of streptococcal pyrogenic exotoxins I and J (SPE-I and SPEJ) from Streptococcus pyogenes, Journal of Immunology 166(11): 6711-6719 (2001) J. Joyce, J. Cook, D. Chabot, R. Hepler, W. Shoop, Q. Xu, T. Stambaugh, M. Aste-Amezaga, S. Wang, L. Indrawati, M. Bruner, A. Friedlander, P. Keller, M. Caulfield: Immunogenicity and protective efficacy Immunogenicity and protective efficacy of Bacillus anthracis poly-gamma-D-glutamic acid capsule covalently of Bacillus anthracis poly-gamma-Dglutamic acid capsule covalently coupled coupled to a protein carrier using a novel triazine-based to a protein carrier using a novel triazine- conjugation strategy, The Journal of Biological Chemistry 281(8): 4831-4843 (2005) based conjugation strategy Z. Jin, G. A. Bohach, J. Shiloach, S. E. Norris, D. I. Conjugates of Group A and W135 Freedberg, C. Deobald, B. Coxon, J. B. Robbins, R. Schneerson: Conjugates of Group A and W135 capsular capsular polysaccharides of neisseria meningitidis bound to recombinant polysaccharides of neisseria meningitidis bound to recombinant staphylococcus aureus enterotoxin c1: staphylococcus aureus enterotoxin c1: preparation, physicochemical preparation, physicochemical characterization, and immunological properties in mice, Infection and Immunity characterization, and immunological properties in mice 73(12): 7887-7893 (2005) Z.-S. Qiao, M. Kim, B. Reinhold, D. Montefiori, J. Wang, E. Design, Expression, and Immunogenicity L. Reinherz: Design, Expression, and Immunogenicity of a Soluble HIV Trimeric Envelope Fragment Adopting a of a Soluble HIV Trimeric Envelope Fragment Adopting a Prefusion Prefusion gp41Configuration, The Journal of Biological Chemistry 20(24): 23138-23146 (2005) gp41Configuration Immunological and biochemical characterization of streptococcal pyrogenic exotoxins I and J (SPE-I and SPE-J) from Streptococcus pyogenes Page 40 of 46 AAPS Focus Group Aggregation and Biological Consequences Literature Collection Version 30 July 2010 5 Immunogenicity observation - acute and/or sporadic 5.1 Aggregate/Particle and molecular structure Data Source In vitro Substance Class Further substance classification / Substance name Corresponding author / Group head Nano-carriers Steele Title Dendrimeric Alkylated Polyethylenimine Nano-carriers with Acid-Cleavable Outer Cationic Shells Mediate Improved Transfection Efficiency Without Increasing Toxicity Full citation T. W. J. Steele, W. T. Shier: Dendrimeric Alkylated Polyethylenimine Nano-carriers with Acid-Cleavable Outer Cationic Shells Mediate Improved Transfection Efficiency Without Increasing Toxicity, Pharmaceutical Research 27(4): 683-698 (2010) 5.2 Aggregate/Particle and long-term storage N/A 5.3 Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t N/A 5.4 Aggregate/Particle detection/characterization N/A 5.5 Immunogenicity observation - chronic and/or general N/A 5.6 Immunogenicity assays N/A Page 41 of 46 AAPS Focus Group Aggregation and Biological Consequences Literature Collection Version 30 July 2010 6 Immunogenicity observation - chronic and/or general 6.1 Aggregate/Particle and molecular structure Data Source No experimental data Substance Class Further substance classification / Substance name Antibody therapeutic proteins Corresponding author / Group head Title Structure-immunogenicity realtionships of therapeutic Hermeling Suzanne proteins Full citation Hermeling S., Crommelin D. J. A., Schellekens H., Jiskoot W.: Structure-immunogenicity realtionships of therapeutic proteins, Pharmaceutical Research 21: 897-903 (2004) 6.2 Aggregate/Particle and long-term storage N/A 6.3 Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t N/A 6.4 Aggregate/Particle detection/characterization Data Source In vitro In vivo animal Substance Class Antibody Protein Further substance classification / Substance name Ig Interferon Alpha Corresponding author / Group head Title Kafi Maleimide conjugation markedly enhances the immunogenicity of both human and murine idiotype-KLH vaccines Braun Andrea Protein aggregates seem to play a key role among the parameters influencing the antigenicity of interferon alpha in normal and transgenis mice 6.5 Immunogenicity observation - acute and/or sporadic N/A Page 42 of 46 Full citation K. Kafi, D. J. Betting, R. E. Yamada, M. Bacica, K. K. Steward, J. M. Timmerman: Maleimide conjugation markedly enhances the immunogenicity of both human and murine idiotype-KLH vaccines, Molecular Immunology 46(3): 448-456 (2009) Braun A., Kwee L., Labow M. A. and Alsenz J.:Protein aggregates seem to play a key role among the parameters influencing the antigenicity of interferon alpha in normal and transgenis mice, Pharmaceutical Research 14: 14721478 (1997) AAPS Focus Group Aggregation and Biological Consequences Literature Collection 6.6 Immunogenicity assays N/A Page 43 of 46 Version 30 July 2010 AAPS Focus Group Aggregation and Biological Consequences Literature Collection Version 30 July 2010 7 Immunogenicity assays Data Source Substance Class Further substance classification / Substance name Corresponding author / Group head In vitro Protein Melan-A/MART-1 Adamina Title Full citation M. Adamina, M. Bolli, F. Albo, A. Cavazza, P. Zajac, E. Padovan, Encapsulation into sterically R. Schumacher, A. Reschner, C. Feder, W. R. Marti, D. Oertli, M. Heberer, G. C. Spagnoli: Encapsulation into sterically stabilised stabilised liposomes enhances the immunogenicity of melanoma- liposomes enhances the immunogenicity of melanoma-associated Melan-A/MART-1 epitopes, British Journal of Cancer 90(1): 263associated Melan-A/MART-1 epitopes 269 (2004) 7.1 Aggregate/Particle and molecular structure Data Source Substance Class In vitro Further substance classification / Substance name Corresponding author / Group head Poly(amido amine)s Wang Title Synthesis and Gene Delivery of Poly(amido amine)s with Different Branched Architecture Full citation R. Wang, L. Zhou, Y. Zhou, G. Li, X. Zhu, H. Gu, X. Jiang, H. Li, J. Wu, L. He, X. Guo, B. Zhu, D. Yan: Synthesis and Gene Delivery of Poly(amido amine)s with Different Branched Architecture, Biomacromolecules 11(2): 489-495 (2010) 7.2 Aggregate/Particle and long-term storage N/A 7.3 Aggregate/Particle and exposure to surfaces/materials/phys. stress/f-t Data Source In vivo animal Substance Class Further substance classification / Substance name Corresponding author / Group head Title Protein human growth hormone Amber Haynes Fradkin Immunogenicity of aggregates of recombinant human growth hormone in mouse models Page 44 of 46 Full citation Fradkin A. H., Carpenter J. F., Randolph T. W.: Immunogenicity of aggregates of recombinant human growth hormone in mouse models, JPS 98: 3247-3264 (2009) AAPS Focus Group Aggregation and Biological Consequences Literature Collection Version 30 July 2010 7.4 Aggregate/Particle detection/characterization Data Source Substance Class Further substance classification / Substance name Corresponding author / Group head In vitro Protein Hemagglutinin Wei In vivo animal Protein Plasmodium falciparum proteins Qian In vitro Antibody anti-p185HER-2 In vitro, In vivo animal Peptid Kubetzko Li Title Comparative Efficacy of Neutralizing Antibodies Elicited by Recombinant Hemagglutinin Proteins from Avian H5N1 Influenza Virus Full citation C.-J. Wei, L. Xu, W.-P. Kong, W. Shi, K. Canis, J. Stevens, Z.-Y. Yang, A. Dell, S. M. Haslam, I. A. Wilson, G. J. Nabel: Comparative Efficacy of Neutralizing Antibodies Elicited by Recombinant Hemagglutinin Proteins from Avian H5N1 Influenza Virus, Journal of Virology 82(13): 6200-6208 (2008) F. Qian, Y. Wu, O. Muratova, H. Zhou, G. Dobrescu, P. Duggan, Conjugating recombinant proteins L. Lynn, G. Song, Y. Zhang, K. Reiter, N. MacDonald, D. L. Narum, C. A. Long, L. H. Miller, A. Saul, G. E. D. Mullen: to Pseudomonas aeruginosa ExoProtein A: A strategy for Conjugating recombinant proteins to Pseudomonas aeruginosa ExoProtein A: A strategy for enhancing immunogenicity of enhancing immunogenicity of malaria vaccine candidates malaria vaccine candidates, Vaccine 25(20): 3923-3933 (2007) Protein PEGylation decreases S. Kubetzko, C. A. Sarkar, A. Plueckthun: Protein PEGylation observed target association rates decreases observed target association rates via a dual blocking via a dual blocking mechanism mechanism, Molecular Pharmacology 68: 1439-1454 (2005) S. W. Li, J. Zhang, Y. M. Li, S. H. Ou, G. Y. Huang, Z. Q. He, S. A bacterially expressed particulate X. Ge, Y. L. Xian, S. Q. Pang, M. H. Ng, N. S. Xia: A bacterially hepatitis E vaccine: antigenicity, expressed particulate hepatitis E vaccine: antigenicity, immunogenicity and protectivity on primates, Vaccine 23(22): immunogenicity and protectivity on primates 2893-2901 (2005) 7.5 Immunogenicity observation - acute and/or sporadic N/A 7.6 Immunogenicity observation - chronic and/or general Data Source In vivo animal No experimental data Substance Class Further substance Corresponding classification / Substance author / Group name head Title Protein Protein therapeutics Coen Maas Protein Biopharmaceuticals Huub Schellekens A Role for Protein Misfolding in immunogenicity of Biopharmaceuticals Bioequivalence and the immunogenicty of biopharmaceuticals Page 45 of 46 Full citation Maas C.,Hermeling s., Bouma B., Jiskoot W., Gebbink M. F. G.: A Role for Protein Misfolding in immunogenicity of Biopharmaceuticals, JBC Papers 282:2229-2236 (2006) Huub Schellekens:Bioequivalence and the immunogenicty of biopharmaceuticals, Nature Reviews 1:457-462 (2002) AAPS Focus Group Aggregation and Biological Consequences Literature Collection In vivo animal Please select Polymere Dintzis H. M. Version 30 July 2010 Dintzis H. M., Dintzis R. Z., Vogelstein B.: Molecular Molecular determinants of determinants of immunogenicity: The immunonn model immunogenicity: The immunonn of immune response, Proc, Natl. Acad. Sci. 73:3671model of immune response 3675 (1976) Page 46 of 46
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