Abstract
The rational development of stable protein formulations requires a detailed understanding of the factors influencing the different routes of protein degradation. Aggregation, one of the major routes of protein degradation, is dependent on, among other factors, the conformational stability of the molecule. Assessing the conformational structure and the factors that affect it, usually via spectroscopic and calorimetric methods, is increasingly used in formulation development to better understand the influence of formulation variables on protein folding and/or aggregation.
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References
1. S. Hermeling, D. J. A. Crommelin, H. Schellekens, and W. Jiskoot, Structure-immunogenicity relationships of therapeutic proteins, Pharm. Res. 21, 897–903 (2004).
2. H. Schellekens, Immunogenicity of therapeutic proteins: Clinical implications and future prospects, Clin. Ther. 24, 1729–1740 (2002).
3. C. E. Glatz, Modeling of aggregation-precipitation phenomena, in: Stability of Protein Pharmaceuticals, Part A: Chemical and Physical Pathways of Protein Degradation, ed. T. E. Ahern and M. C. Manning (New York: Plenum Press, 1992), 135–166.
4. W. Wang and D. N. Kelner, Correlation of rFVIII inactivation with aggregation in solution, Pharm. Res. 20, 693–700 (2003).
5. R. W. Carrell and D. W. Lomas, Conformational disease, Lancet 350, 134–138 (1997).
6. R. Krishnamurthy and M. C. Manning, The stability factor: Importance in formulation development, Curr. Pharm. Biotechnol. 3, 361–371 (2002).
7. B. S. Kendrick, J. L. Cleland, X. Lam, T. Nguyen, T. W. Randolph, M. C. Manning, and J. F. Carpenter, Aggregation of recombinant human interferon gamma: Kinetics and structural transitions, J. Pharm. Sci. 87, 1069–1076 (1998).
8. E. Y. Chi, S. Krishnan, T. W. Randolph, and J. F. Carpenter, Physical stability of proteins in aqueous solution: Mechanism and driving forces in nonnative protein aggregation, Pharm. Res. 20(9): 1325–1336 (2003).
9. R. Lumry and H. Eyring, Conformational changes of proteins, J. Phys. Chem. 58, 110–120 (1954).
10. D. Xie and E. Freire, Molecular basis of cooperativity in protein folding. V. Thermodynamic and structural conditions for the stabilization of compact denatured states, Proteins: Struct. Funct. Genet. 19, 291–301 (1994).
11. A. L. Fink, L. J. Calciano, Y. Goto, T. Kurotsu, and D. R. Palleros, Classification of acid denaturation of proteins: Intermediates and unfolded states, Biochem. 33, 12504–12511 (1994).
12. O. B. Ptitsyn, V. E. Bychkova, and V. N. Uversky, Kinetic and equilibrium folding intermediates, Phil. Trans. Roy. Soc. Lond. B Biol. Sci. 348, 35–41 (1995).
13. L. A. Kueltzo and Middaugh, C.R., Structural characterization of bovine granulocyte colony stimulating factor: Effect of temperature and pH, J. Pharm. Sci. 92, 1793–1804 (2003).
14. J. E. Matsuura, A. E. Morris, R. R. Ketchem, E. H. Braswell, R. Klinke, W. R. Gombotz, and R. L. Remmele, Jr., Biophysical characterization of a soluble CD40 ligand (CD154) coiled-coil trimer: Evidence of a reversible acid-denatured molten globule, Arch. Biochem. Biophy. 392(2), 208–218 (2001).
15. A. L. Fink, Protein aggregation: Folding aggregates, inclusion bodies, and amyloid, Folding Des. 3, R9–R23 (1998).
16. G. P. Privalov and P. L. Privalov, Problems and prospects in microcalorimetry of biological macromolecules, J. Mol. Biol. 323, 31–62 (2000).
17. C. N. Pace and K. L. Shaw, Linear extrapolation method of analyzing solvent denaturation curves, Proteins: Struct. Funct. Genet. S4, 1–7 (2000).
18. M. J. Treuheit, A. A. Kosky, and D. N. Brems, Inverse relationship of protein concentration and aggregation, Pharm. Res. 19, 511–516 (2002).
19. P. L. Privalov, Stability of proteins: Small globular proteins, Adv. Prot. Chem. 33, 167–241 (1979).
20. P. L. Privalov and S. A. Potekhin, Scanning microcalorimetry in studying temperature-induced changes in proteins, Meth. Enzymol. 131, 4–51 (1986).
21. E. Freire, Thermal denaturation methods in the study of protein folding, Meth. Enzymol. 259, 144–168 (1995).
22. R. L. Remmele, Jr., N. S. Nightlinger, S. Srinivasan, and W. R. Gombotz, Interleukin-1 receptor (IL-1R) liquid formulation development using differential scanning calorimetry, Pharm. Res. 15(2), 200–208 (1998).
23. M. Roberge, R. N. A. H. Lewis, F. Shareck, R. Morosoli, D. Kluepfel, C. Dupont, and R. N. McElhaney, Differential scanning calorimetric, circular dichroism, and Fourier transform infrared spectroscopic characterization of the thermal unfolding of Xylanase A from Streptomyces lividans, Proteins: Struct. Funct. Genet. 50, 341–354 (2003).
24. M. Cueto, M. J. Dorta, O. Munguia, and M. Llabres, New approach to stability assessment of protein solution formulations by differential scanning calorimetery, Int. J. Pharm. 252, 159–166 (2003).
25. M. Cauchy, S. D'Aoust, B. Dawson, H. Rode, and M. A. Hefford, Thermal stability: A means to assure tertiary structure in therapeutic proteins, Biological 30, 175–185 (2002).
26. K. Tsumoto, K. Ogasahara, Y. Ueda, K. Watanabi, K. Yutani, and I. Kumagai, Role of salt-bridge formation in antigen-antibody interaction. Entropic contribution to the complex between hen egg white lysozyme and its monoclonal antibody HyHEL10, J. Biol. Chem. 271, 32612–32616 (1996).
27. S. L. Clugston, R. Yajima, and J. F. Honek, Investigation of metal binding and activation of Escherichia coli glycoxalase I: Kinetic, thermodynamic, and mutagenesis studies, Biochem. J. 377, 309–316 (2004).
28. D. K. Chou, R. Krishnamurthy, T. W. Randolph, J. C. Carpenter, and M. C. Manning, Effects of Tween 20 on the stability of Albutropin during agitation, AAPS National Biotechnology meeting, Boston, 2004.
29. M. M. Pierce, C. S. Raman, and B. T. Nall, Isothermal titration calorimetry of protein-protein interactions, Methods 19, 213–221 (1999).
30. S. W. Dodd, H. A. Havel, P. M. Kovach, C. Lakshminarayan, M. P. Redmon, C. M. Sargeant, G. R. Sullivan, and J. M. Beals, Reversible adsorption of soluble hexameric insulin onto the surface of insulin crystals cocrystallized with protamine: An electrostatic interaction, Pharm. Res. 12, 60–68 (1995).
31. M. M. Santoro and D. W. Bolen, Unfolding free energy changes determined by the linear extrapolation method. 1. Unfolding of phenylmethanesulfonyl α-chymotrypsin using different denaturants, Biochemistry 27, 8063–8068 (1988).
32. S. J. Shire, L. A. Holladay, and E. Rinderknecht, Self-association of human and porcine Relaxin as assessed by analytical ultracentrifugation and circular dichroism, Biochemistry 30, 7703–7711 (1991).
33. J. F. Carpenter, S. J. Prestrelski, and A. Dong, Application of infrared spectroscopy to development of stable lyophilized protein formulations, Eur. J. Pharm. Biopharm. 45, 231–238 (1998).
34. S. T. Tzannis, W. J. M. Hrushesky, P. A. Wood, and T. M. Przybycien, Irreversible inactivation of interleukin-2 in a pump-based delivery environment, Proc. Nat. Acad. Sci. USA 93, 5460–5465 (1996).
35. G. Zuber, S. J. Prestrelski, and K. Benedek, Application of Fourier transform infrared spectroscopy to studies of aqueous protein solutions, Anal. Biochem. 207, 150–156 (1992).
36. A. Dong, S. J. Prestrelski, S. D. Allison, and J. F. Carpenter, Infrared spectroscopic studies of lyophilization- and temperature-induced protein aggregation, J. Pharm. Sci. 84(4), 415–424 (1995).
37. B. S. Kendrick, A. Dong, S. D. Allison, M. C. Manning, and J. C. Carpenter, Quantitation of the area of overlap between second-derivative amide I infrared spectra to determine structural similarity of a protein in different states, J. Pharm. Sci. 85(2), 155–158 (1996).
38. S. J. Prestrelski, T. Arakawa, and J. F. Carpenter, Separation of freezing-and drying-induced denaturation of lyophilized proteins using stress-specific stabilization II. Structural studies using infrared spectroscopy, Arch. Biochem. Biophys. 303(2), 465–473 (1993).
39. B. S. Kendrick, B. S. Chang, T. Arakawa, B. Peterson, T. W. Randolph, M. C. Manning, and J. C. Carpenter, Preferential exclusion of sucrose from recombinant interleukin-1 receptor antagonist: Role in restricted conformational mobility and compaction of native state, Proc. Natl. Acad. Sci. USA 94, 11917–11922 (1997).
40. E. Y. Chi, S. Krishnan, B. S. Kendrick, B.S. Chang, J. F. Carpenter, and T. W. Randolph, Roles of conformational stability and colloidal stability in the aggregation of recombinant human granulocyte colony-stimulating factor, Prot. Sci. 12, 903–913 (2003).
41. S. Krishnan, E. Y. Chi, J. N. Webb, B. S. Chang, D. Shan, M. Goldenberg, M. C. Manning, T. W. Randolph, and J. F. Carpenter, Aggregation of granulocyte colony-stimulating factor under physiological conditions: Characterization and thermodynamic inhibition, Biochemistry 41, 6422–6431 (2002).
42. T. Arakawa and Y. Kita, Stabilizing effects of caprylate and acetyltryptophonate on heat-induced aggregation of bovine serum albumin, Biochim. Biophys. Acta, 1479, 32–36 (2000).
43. R. L. Remmele, Jr., S. D. Bhat, D. H. Phan, and W. R. Gombotz, Minimization of recombinant human F1t3 ligand aggregation at the Tm plateau: A matter of thermal reversibility, Biochemistry 38, 5241–5247 (1999).
44. J. C. Lee and S. N. Timasheff, The stabilization of proteins by sucrose, J. Biol. Chem. 256, 7193–7201 (1981).
45. S. N. Timasheff, Control of protein stability and reactions by weakly interacting cosolvents: The simplicity of the complicated, Adv. Prot. Chem. 51, 355–432 (1998).
46. Y. Kim, L. S. Jones, A. Dong, B. S. Kendrick, B. S. Chang, M. C. Manning, T. W. Randolph, and J. F. Carpenter, Effects of sucrose on conformational equilibria and fluctuations within the native-state ensemble of proteins, Prot. Sci. 12, 1252–1261 (2003).
47. J. F. Carpenter, M. J. Pikal, B. S. Chang, and T. W. Randolph, Rational design of stable lyophilized protein formulations: some practical advice, Pharm. Res. 14, 969–975 (1997).
48. J. L. Cleland, X. Lam, B. Kendrick, J. Yang, T. Yang, D. Overcashier, D. Brooks, C. Hsu, and J. F. Carpenter, A specific molar ratio of stabilizer to protein is required for storage stability of a lyophilized monoclonal antibody, J. Pharm. Sci. 90(3), 310–321 (2000).
49. V. Hlady, J. Buijs, and H. P. Jennissen, Methods for studying protein adsorption, Meth. Enzymol. 309, 402–429 (1999).
50. M. A. Carignano and I. Szleifer, Prevention of protein adsorption by flexible and rigid chain molecules, Colloids Surf. B: Biointerfaces 18, 169–182 (2000).
51. F. Zhang, E. T. Kang, K. G. Neoh, P. Wang, and K. L. Tan, Surface modification of stainless steel by grafting of poly(ethylene glycol) for reduction in protein adsorption, Biomaterials 22, 1541–1548 (2001).
52. M. A. Ruegsegger and R. E. Marchant, Reduced protein adsorption and platelet adhesion by controlled variation of oligomaltose surfactant polymer coatings, J. Biomed. Mater. Res. 56, 159–167 (2001).
53. T. Hasegawa, Y. Iwasaki, and K. Ishihara, Preparation and performance of protein-adsorption-resistant asymmetric porous membrane composed of polysulfone/phospholipid polymer blend, Biomaterials 22, 243–251 (2001).
54. X. M. Lam, T. W. Patapoff, and T. H. Nguyen, The effect of benzyl alcohol on recombinant human interferon-γ, Pharm. Res. 14, 725–729 (1997).
55. B. Chen, T. Arakawa, E. Hsu, L. O. Narhi, T. J. Tressel, and S. L. Chien, Strategies to suppress aggregation of recombinant keratinocyte growth factor during liquid formulation development, J. Pharm. Sci. 83(12), 1657–1661 (1994).
56. Y. Kita and T. Arakawa, Salts and glycine increase reversibility and decrease aggregation during thermal unfolding of ribonuclease-A, BioSci. Biotechnol. Biochem. 66, 880–882 (2002).
57. T. Ueda, M. Nagata, and T. Imoto, Aggregation and chemical reaction in hen lysozyme caused by heating at pH 6 are depressed by osmolytes, sucrose and trehalose, J. Biochem. (Tokyo) 130, 491–496 (2001).
58. B. S. Chang, R. M. Beauvais, A. Dong, and J. F. Carpenter, Physical factors affecting the storage stability of freeze-dried interleukin-1 receptor antagonist: Glass transition and protein conformation, Arch. Biochem. Biophys. 331(2), 249–258 (1996).
59. S. J. Prestrelski, K. A. Pikal, and T. Arakawa, Optimization of lyophilization conditions for recombinant human interleukin-2 by dried state conformational analysis using Fourier-transform infrared spectroscopy, Pharm. Res. 12(9), 1250–1259 (1995).
60. Y. Liao, M. B. Brown, A. Quader, and G. P. Martin, Protective mechanism of stabilizing excipients against dehydration in the freeze-drying of proteins, Pharm. Res. 19(12), 1852–1861 (2002).
61. L. Kreilgaard, S. Frokjaer, J. M. Flink, T. W. Randolph, and J. F. Carpenter, Effect of additives on the stability of Humicola langinosa lipase during freeze-drying and storage in the dried solid, J. Pharm. Sci. 88(3), 281–290 (1999).
62. S. D. Allison, M. C. Manning, T. W. Randolph, K. Middleton, A. Davis, and J. F. Carpenter, Optimization of storage stability of lyophilized actin using combinations of disaccharides and dextran, J. Pharm. Sci. 89(2), 199–214 (2000).
63. R. L. Remmele, Jr., C. Stushnoff, and J. F. Carpenter, Real-time in situ monitoring of lysozyme during lyophilization using infrared spectroscopy: Dehydration stress in the presence of sucrose, Pharm. Res. 14(11), 1548–1555 (1997).
64. J. D. Andya, C. C. Hsu, and S. J. Shire, Mechanisms of aggregate formation and carbohydrate excipient stabilization of lyophilized humanized monoclonal antibody formulations, AAPS Pharm. Sci. 5(2), 1–11 (2003).
65. J. Fransson, D. Hallen, and E. Florin-Robertsson, Solvent effects on the solubility and physical stability of human insulin-like growth factor I, Pharm. Res. 14, 606–612 (1997).
66. S. D. Webb, J. L. Cleland, J. F. Carpenter, and T. W. Randolph, Effect of annealing lyophilized and spray-lyophilized formulations of recombinant human interferon-gamma, J. Pharm. Sci. 92, 715–729 (2003).
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Wilcox, A., Krishnamurthy, R. (2006). Application of Spectroscopic and Calorimetric Techniques in Protein Formulation Development. In: Misbehaving Proteins. Springer, New York, NY. https://doi.org/10.1007/978-0-387-36063-8_5
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DOI: https://doi.org/10.1007/978-0-387-36063-8_5
Publisher Name: Springer, New York, NY
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