Christian Rischel and Matthías Thórólfsson are employees of Novo Nordisk A/S, which develops, manufactures and markets therapeutic proteins.
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Aggregation of a multidomain protein: A coagulation mechanism governs aggregation of a model IgG1 antibody under weak thermal stress
Article first published online: 15 DEC 2009
DOI: 10.1002/pro.309
Copyright © 2009 The Protein Society
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How to Cite
Andersen, C. B., Manno, M., Rischel, C., Thórólfsson, M. and Martorana, V. (2010), Aggregation of a multidomain protein: A coagulation mechanism governs aggregation of a model IgG1 antibody under weak thermal stress. Protein Science, 19: 279–290. doi: 10.1002/pro.309
Publication History
- Issue published online: 21 JAN 2010
- Article first published online: 15 DEC 2009
- Accepted manuscript online: 15 DEC 2009 12:00AM EST
- Manuscript Accepted: 30 NOV 2009
- Manuscript Received: 7 OCT 2009
Funded by
- Novo Nordisk International Postdoc Fellowship (C.B.A.)
References
- 1, , , ( 2003) Physical stability of proteins in aqueous solution: mechanism and driving forces in nonnative protein aggregation. Pharm Res 20: 1325–1336.
- 2( 2003) Protein folding and misfolding. Nature 426: 884–890.
- 3, , , , , , ( 2009) Protein stability modulated by a conformational effector: effects of trifluoroethanol on bovine serum albumin. Phys Chem Chem Phys 11: 4007–4018.
- 4, ( 2005) Protein drug stability: a formulation challenge. Nat Rev Drug Discov 4: 298–306.
- 5, , , , ( 2008) Heterogeneity of monoclonal antibodies. J Pharm Sci 97: 2426–2447.Direct Link:
- 6, , , , , , , ( 2006) Real-time and single fibril observation of the formation of amyloid β spherulitic structures. J Biol Chem 281: 33677–33683.
- 7, , ( 2006) Solvation-assisted pressure tuning of insulin fibrillation: from novel aggregation pathways to biotechnological applications. J Mol Biol 356: 497–509.
- 8, , ( 2005) Protein particulates: another generic form of protein aggregation? Biophys J 92: 1336–1342.
- 9, , , , ( 1996) On the nucleation and growth of amyloid β-protein fibrils: detection of nuclei and quantitation of rate constants. Proc Natl Acad Sci USA 93: 1125–1129.
- 10, , ( 1993) Aggregation of globular proteins. Acc Chem Res 26: 614–620.
- 11( 2007) Non-native protein aggregation kinetics. Biotechnol Bioeng 98: 927–938.Direct Link:
- 12, , , ( 1998) A transient expansion of the native state precedes aggregation of recombinant human interferon-γ. Proc Natl Acad Sci USA 95: 14142–14146.
- 13, , , , ( 2007) Antibody structure, instability, and formulation. J Pharm Sci 96: 1–26.Direct Link:
- 14, , , , , , ( 2005) Structural characterization and immunogenicity in wild-type and immune tolerant mice of degraded recombinant human interferon alpha2b. Pharm Res 22: 1997–2006.
- 15, ( 2007) Immunogenicity of protein therapeutics. Trends Immunol 28: 482–490.
- 16( 2006) Effects of protein aggregates: an immunologic perspective. AAPS J 8: E501–E507.
- 17, , , ( 2004) From the bench to the bedside: ways to improve rituximab efficacy. Blood 104: 2635–2642.
- 18, , ( 1984) Scaling behavior and cluster fractal dimension determined by light scattering from aggregating proteins. Phys Rev Lett 53: 1403–1406.
- 19
- 20, , , ( 2008) Shaken, not stirred: mechanical stress testing of an IgG1 antibody. J Pharm Sci 97: 4347–4366.Direct Link:
- 21, , , , ( 2005) Induction and analysis of aggregates in a liquid IgG1-antibody formulation. Eur J Pharm Biopharm 59: 407–417.
- 22, , , , , , , , , , , ( 2006) Active dimer of Epratuzumab provides insight into the complex nature of an antibody aggregate. J Pharm Sci 95: 126–145.Direct Link:
- 23, , , ( 1986) Characterization of a heat-stable fraction of human IgG. J Prot Chem 5: 323–333.
- 24, , , , ( 2009) Elucidation of two major aggregation pathways in an IgG2 antibody. J Pharm Sci 98: 3013–3030.Direct Link:
- 25, , ( 2009) Characterization of high-molecular-weight nonnative aggregates and aggregation kinetics by size exclusion chromatography with inline multi-angle laser light scattering. J Pharm Sci 98: 3997–4017.Direct Link:
- 26, , , ( 2000) Characterization and isolation of intermediates in β-lactoglobulin heat aggregation at high pH. Biophys J 79: 1030–1038.
- 27( 1999) Analysis of protein aggregation kinetics. Methods Enzymol 309: 256–274.
- 28, ( 2008) Amyloid—a state in many guises: survival of the fittest fibril fold. Protein Sci 17: 2–10.Direct Link:
- 29, ( 2007) A broad range of Fab stabilities within a host of therapeutic IgGs. Biochem Biophys Res Commun 355: 751–757.
- 30, , , ( 2008) Contribution of variable domains to the stability of humanized IgG1 monoclonal antibodies. J Pharm Sci 97: 1414–1426.Direct Link:
- 31, ( 2008) Antibody therapeutics, antibody engineering, and the merits of protein stability. Curr Opin Drug Discov Dev 11: 675–687.
- 32( 1992) Thereotical analysis of Lumry-Eyring models in differential scanning calorimetry. Biophys J 61: 921–935.
- 33, ( 2000) The thermal stability of immunoglobulin: unfolding and aggregation of a multi-domain protein. Biophys J 78: 394–404.
- 34
- 35, , , ( 1988) Differential scanning calorimetry of the irreversible thermal denaturation of thermolysin. Biochemistry 27: 1648–1652.
- 36, , , ( 2007) Highly concentrated monoclonal antibody solutions: direct analysis of physical structure and thermal stability. J Pharm Sci 96: 532–546.Direct Link:
- 37, ( 1967) Theory of critical-point scattering and correlations. I. The Ising model. Phys Rev 156: 583–622.
- 38, , ( 1994) Structure and distribution of aggregates formed after heat-induced denaturation of globular proteins. Macromolecules 27: 583–589.
- 39, , , ( 1998) Analysis of aggregate structure in food protein gels with the concept of fractal. Biosci Biotechnol Biochem 61: 1663–1667.
- 40, , , , ( 2005) Protofibril formation of amyloid β-protein at low pH via a non-cooperative elongation mechanism. J Biol Chem 280: 30001–30008.
- 41, , ( 1999) Kinetics of aggregation and gelation of globular proteins after heat-induced denaturation. Macromolecules 32: 6120–6127.
- 42, , , ( 1987) Universal kinetics in reaction-limited aggregation. Phys Rev Lett 58: 274–277.
- 43, ( 1990) Variable aggregation rates in colloidal gold: kernel homogeneity dependence on aggregant concentration. Phys Rev A 41: 2093–2100.
- 44, , , , , , , , ( 2009) Branching in amyloid fibril growth. Biophys J 96: 1529–1536.
- 45, , , , , , , ( 2007) Kinetics of different processes in human insulin amyloid formation. J Mol Biol 366: 258–274.
- 46( 2000) Approximate population balance equations for aggregation-breakage processes. J Colloid Interface Sci 221: 143–160.
- 47, , ( 1999) Kinetic study on thermal denaturation of hen egg-white lysozyme involving precipitation. J Biosci Bioeng 87: 199–205.
- 48, ( 2005) The kinetic behavior of insulin fibrillation is determined by heterogeneous nucleation pathways. Protein Sci 14: 3129–3134.Direct Link:
- 49, , , ( 1981) Intrinsically stable IgG aggregates. J Immunol Methods 41: 63–74.
- 50, , , , , ( 2006) Protein structural conformation and not second virial coefficient relates to long-term irreversible aggregation of a monoclonal antibody and ovalbumin in solution. Pharm Res 23: 1382–1394.
- 51, , ( 2000) Lower kinetic limit to protein thermal stability: a proposal regarding protein stability in vivo and its relation with misfolding diseases. Proteins 40: 58–70.Direct Link:
- 52( 2001) Revisiting the method of cumulants for the analysis of dynamic light-scattering data. Appl Opt 40: 4087–4091.
- 53
- 54, , , , , , , , , ( 2001) Crystal structure of a neutralizing human IgG against HIV-1: a template for vaccine design. Science 293: 1155–1159.
- 55, ( 2008) Gwyddion 2.10 SPM data analysis program. Available at: http://gwyddion.net. Accessed October 2009.
- 56, , ( 2008) Extrinsic fluorescent dyes as tools for protein characterization. Pharm Res 25: 1487–1499.
- 57, , , , , , , , , , ( 2001) High-density miniaturized thermal shift assays as a general strategy for drug discovery. J Biomol Screen 6: 429–440.

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