Advertisement

Pharmaceutical Research

, Volume 20, Issue 9, pp 1325–1336 | Cite as

Physical Stability of Proteins in Aqueous Solution: Mechanism and Driving Forces in Nonnative Protein Aggregation

  • Eva Y. Chi
  • Sampathkumar Krishnan
  • Theodore W. Randolph
  • John F. Carpenter
Article

Abstract

Irreversible protein aggregation is problematic in the biotechnology industry, where aggregation is encountered throughout the lifetime of a therapeutic protein, including during refolding, purification, sterilization, shipping, and storage processes. The purpose of the current review is to provide a fundamental understanding of the mechanisms by which proteins aggregate and by which varying solution conditions, such as temperature, pH, salt type, salt concentration, cosolutes, preservatives, and surfactants, affect this process.

formulation pharmaceuticals denaturation second virial coefficient conformational stability 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    H. Wu. Studies on the denaturation of proteins, XIII. A theory of denaturation. Chinese J. Physiol. 5:321–344 (1931).Google Scholar
  2. 2.
    J. T. Edsall. Hsien Wu and the first theory of protein denaturation (1931). Adv. Protein Chem. 46:1–5 (1995).Google Scholar
  3. 3.
    R. Lumry and H. Eyring. Conformation changes of proteins. J. Phys. Chem. 58:110–120 (1954).Google Scholar
  4. 4.
    PhRMA. The promise of breakthroughs in biotechnology is bright with 369 biotechnology medicines with testing. http://www.phrma.org 2000.Google Scholar
  5. 5.
    J. L. Cleland, M. F. Powell, and S. J. Shire. The development of stable protein formulations—a close look at protein aggregation, deamidation and oxidation. Crit. Rev. Ther. Drug 10:307–377 (1993).Google Scholar
  6. 6.
    M. C. Manning, K. Patel, and R. T. Borchardt. Stability of protein pharmaceuticals. Pharm. Res. 6:903–918 (1989).Google Scholar
  7. 7.
    C. Goolcharran, M. Khossravi, and R. T. Borchardt. Chemical pathways of peptide and protein degradation. In S. Frokjaer and L. Hovgaards (eds.), Pharmaceutical Formulation and Development of Peptides and Proteins, Taylor and Francis, London, 2000, pp. 70–88.Google Scholar
  8. 8.
    J. Brange. Physical stability of proteins. In S. Frokjaer and L. Hovgaards (eds.), Pharmaceutical Formulation and Development of Peptides and Proteins, Taylor and Francis, London, 2000, pp. 89–112.Google Scholar
  9. 9.
    D. B. Volkin and C. R. Middaugh. In T. J. Ahern and M. C. Mannings (eds.), Stability of Protein Pharmaceuticals. Part A: Chemical and Physical Pathways of Protein Degradation, Plenum Press, New York, 1992, p. 215.Google Scholar
  10. 10.
    T. W. Randolph and L. S. Jones. Surfactant–protein interactions. In J. F. Carpenter and M. C. Mannings (eds.), Rational Design of Stable Protein Formulations, Theory and Practice, Kluwer Academic/Plenum Publishers, New York, 2002, p. 198.Google Scholar
  11. 11.
    A. C. Dong, S. J. Prestrelski, S. D. Allison, and J. F. Carpenter. Infrared spectroscopic studies of lyophilization–induced and temperature–induced protein aggregation. J. Pharm. Sci. 84:415–424 (1995).Google Scholar
  12. 12.
    A. Wang, A. D. Robertson, and D. W. Bolen. Effects of a naturally occurring compatible osmolyte on the internal dynamics of ribonuclease–a. Biochemistry 34:15096–15104 (1995).Google Scholar
  13. 13.
    J. F. Carpenter, B. S. Kendrick, B. S. Chang, M. C. Manning, and T. W. Randolph. Inhibition of stress–induced aggregation of protein therapeutics. Methods Enzymol. 309:236–255 (1999).Google Scholar
  14. 14.
    A. L. Fink. Protein aggregation: Folding aggregates, inclusion bodies and amyloid. Fold. Des. 3:R9–R23 (1998).Google Scholar
  15. 15.
    Y.–S. Kim, S. P. Cape, E. Y. Chi, R. Raffen, P. Wilkins–Stevens, F. J. Stevens, M. C. Manning, T. W. Randolph, A. Solomon, and J. F. Carpenter. Counteracting effects of renal solutes on amyloid fibril formation by immunoglobulin light chains. J. Biol. Chem. 276:1626–1633 (2001).Google Scholar
  16. 16.
    Y. F. Maa and C. C. Hsu. Aggregation of recombinant human growth hormone induced by phenolic compounds. Int. J. Pharm. 140:155–168 (1996).Google Scholar
  17. 17.
    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).Google Scholar
  18. 18.
    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).Google Scholar
  19. 19.
    Y.–S. Kim, J. S. Wall, J. Meyer, C. Murphy, T. W. Randolph, M. C. Manning, and J. F. Carpenter. Thermodynamic modulation of light chain amyloid fibril formation. J. Biol. Chem. 276:1570–1574 (2000).Google Scholar
  20. 20.
    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. Protein Sci. 12:903–913 (2003).Google Scholar
  21. 21.
    K. A. Dill. Dominant forces in protein folding. Biochemistry 29:7133–7155 (1990).Google Scholar
  22. 22.
    C. N. Pace, B. A. Shirley, M. McNutt, and K. Gajiwala. Forces contributing to the conformational stability of proteins. FASEB J. 10:75–83 (1996).Google Scholar
  23. 23.
    R. Jaenicke. In R. Huber and E. L. Winnackers (eds.), Protein Structure and Protein Engineering, Springer Verlag, Berlin, 1988, pp. 16–36.Google Scholar
  24. 24.
    R. Jaenicke and R. Rudolph. In T. E. Creightons (ed.), Protein Structure: A Practical Approach, IRL Press, Oxford, 1989, pp. 191–223.Google Scholar
  25. 25.
    R. Jaenicke. Protein folding: Local structures, domains, subunits, and assemblies. Biochemistry 30:3147–3161 (1991).Google Scholar
  26. 26.
    J. Israelachvili. Intermolecular and Surface Forces, Academic Press, San Diego, California, 1992.Google Scholar
  27. 27.
    G. Graziano, F. Catanzano, A. Riccio, and G. Barone. A reassessment of the molecular origin of cold denaturation. J. Biochem. (Tokyo) 122:395–401 (1997).Google Scholar
  28. 28.
    N. T. Southall, K. A. Dill, and A. D. J. Haymet. A view of the hydrophobic effect. J. Phys. Chem. B 106:521–533 (2002).Google Scholar
  29. 29.
    P. L. Privalov. Cold denaturation of proteins. Crit. Rev. Biochem. Mol. Biol. 25:281–305 (1990).Google Scholar
  30. 30.
    P. L. Privalov and S. J. Gill. Stability of protein structure and hydrophobic interaction. Adv. Protein Chem. 39:191–234 (1988).Google Scholar
  31. 31.
    C. N. Pace. Polar group burial contributes more to protein stability than nonpolar group burial. Biochem. 40:310–313 (2001).Google Scholar
  32. 32.
    R. L. Remmele, S. D. Bhat, D. H. Phan, and W. R. Gombotz. Minimization of recombinant human flt3 ligand aggregation at the t–m plateau: A matter of thermal reversibility. Biochem. 38:5241–5247 (1999).Google Scholar
  33. 33.
    A. I. Azuaga, C. M. Dobson, P. L. Mateo, and F. Conejero–Lara. Unfolding and aggregation during the thermal denaturation of streptokinase. Eur. J. Biochem. 269:4121–4133 (2002).Google Scholar
  34. 34.
    B. L. 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. 83:1657–1661 (1994).Google Scholar
  35. 35.
    B. L. Chen, T. Arakawa, C. F. Morris, W. C. Kenney, C. M. Wells, and C. G. Pitt. Aggregation pathway of recombinant human keratinocyte growth–factor and its stabilization. Pharm. Res. 11:1581–1587 (1994).Google Scholar
  36. 36.
    A. Y. Ip, T. Arakawa, H. Silvers, C. M. Ransone, and R. W. Niven. Stability of recombinant consensus interferon to air–jet and ultrasonic nebulization. J. Pharm. Sci. 84:1210–1214 (1995).Google Scholar
  37. 37.
    M. G. Mulkerrin and R. Wetzel. pH–dependence of the reversible and irreversible thermal–denaturation of gamma–interferons. Biochem. 28:6556–6561 (1989).Google Scholar
  38. 38.
    A. M. Tsai, J. H. van Zanten, and M. J. Betenbaugh. II. Electrostatic effect in the aggregation of heat–denatured RNase a and implications for protein additive design. Biotechnol. Bioeng. 59:281–285 (1998).Google Scholar
  39. 39.
    A. M. Tsai, J. H. van Zanten, and M. J. Betenbaugh. I. Study of protein aggregation due to heat denaturation: A structural approach using circular dichroism spectroscopy, nuclear magnetic resonance, and static light scattering. Biotechnol. Bioeng. 59:273–280 (1998).Google Scholar
  40. 40.
    P. Atkins. Physical Chemistry, W. H. Freeman and Company, New York, 1994.Google Scholar
  41. 41.
    A. Fatouros, T. Osterberg, and M. Mikaelsson. Recombinant factor VIII SQ–influence of oxygen, metal ions, ph and ionic strength on its stability in aqueous solution. Int. J. Pharm. 155:121–131 (1997).Google Scholar
  42. 42.
    M. Vrkljan, T. M. Foster, M. E. Powers, J. Henkin, W. R. Porter, H. Staack, J. F. Carpenter, and M. C. Manning. Thermal–stability of low–molecular–weight urokinase during heat–treatment.2. Effect of polymeric additives. Pharm. Res. 11:1004–1008 (1994).Google Scholar
  43. 43.
    T. H. Nguyen and S. J. Shire. Stability and characterization of recombinant human relaxin. In R. Pearlman and Y. J. Wangs (eds.), Formulation, Characterization, and Stability of Protein Drugs, Plenum Press, New York, 1996, pp. 211–247.Google Scholar
  44. 44.
    B. A. Kerwin, M. J. Akers, I. Apostol, C. Moore–Einsel, J. E. Etter, E. Hess, J. Lippincott, J. Levine, A. J. Mathews, P. Revilla–Sharp, R. Schubert, and D. L. Looker. Acute and long–term stability studies of deoxy hemoglobin and characterization of ascorbate–induced modifications. J. Pharm. Sci. 88:79–88 (1999).Google Scholar
  45. 45.
    L. C. Gu, E. A. Erdos, H. S. Chiang, T. Calderwood, K. Tsai, G. C. Visor, J. Duffy, W. C. Hsu, and L. C. Foster. Stability of interleukin–1–beta (IL–1–gamma) in aqueous solution — analytical methods, kinetics, products, and solution formulation implications. Pharm. Res. 8:485–490 (1991).Google Scholar
  46. 46.
    M. W. Townsend and P. P. Deluca. Stability of ribonuclease–a in solution and the freeze–dried state. J. Pharm. Sci. 79:1083–1086 (1990).Google Scholar
  47. 47.
    L. Nielsen, R. Khurana, A. Coats, S. Frokjaer, J. Brange, S. Vyas, V. N. Uversky, and A. L. Fink. Effect of environmental factors on the kinetics of insulin fibril formation: Elucidation of the molecular mechanism. Biochemistry 40:6036–6046 (2001).Google Scholar
  48. 48.
    K. Takano, K. Tsuchimori, Y. Yamagata, and K. Yutani. Contribution of salt bridges near the surface of a protein to the conformational stability. Biochemistry 39:12375–12381 (2000).Google Scholar
  49. 49.
    G. R. Grimsley, K. L. Shaw, L. R. Fee, R. W. Alston, B. M. P. Huyghues–Despointes, R. L. Thurlkill, J. M. Scholtz, and C. N. Pace. Increasing protein stability by altering long–range coulombic interactions. Protein Sci. 8:1843–1849 (1999).Google Scholar
  50. 50.
    A. Striolo, D. Bratko, J. Z. Wu, N. Elvassore, H. W. Blanch, and J. M. Prausnitz. Forces between aqueous nonuniformly charged colloids from molecular simulation. J. Chem. Phys. 116:7733–7743 (2002).Google Scholar
  51. 51.
    S. N. Timasheff. Control of protein stability and reactions by weakly interacting cosolvents: The simplicity of the complicated. Adv. Protein Chem. 51:355–432 (1998).Google Scholar
  52. 52.
    P. K. Tsai, D. B. Volkin, J. M. Dabora, K. C. Thompson, M. W. Bruner, J. O. Gress, B. Matuszewska, M. Keogan, J. V. Bondi, and C. R. Middaugh. Formulation design of acidic fibroblast growth–factor. Pharm. Res. 10:649–659 (1993).Google Scholar
  53. 53.
    B. C. Cunningham, M. G. Mulkerrin, and J. A. Wells. Dimerization of human growth–hormone by zinc. Science 253:545–548 (1991).Google Scholar
  54. 54.
    P. R. Davis–Searles, A. J. Saunders, D. A. Erie, D. J. Winzor, and G. J. Pielak. Interpreting the effects of small uncharged solutes on protein–folding equilibria. Annu. Rev. Biophys. Biomol. Struct. 30:271–306 (2001).Google Scholar
  55. 55.
    M. G. Cacace, E. M. Landau, and J. J. Ramsden. The hofmeister series: Salt and solvent effects on interfacial phenomena. Q. Rev. Biophys. 30:241–277 (1997).Google Scholar
  56. 56.
    T. Arakawa and S. N. Timasheff. Stabilization of protein–structure by sugars. Biochemistry 21:6536–6544 (1982).Google Scholar
  57. 57.
    J. C. Lee and S. N. Timasheff. The stabilization of proteins by sucrose. J. Biol. Chem. 256:7193–7201 (1981).Google Scholar
  58. 58.
    R. Sousa. Use of glycerol, polyols, and other protein structure stabilizing agents in protein crystallization. Acta Cryst. D51:271–277 (1995).Google Scholar
  59. 59.
    B. A. Kerwin, M. C. Heller, S. H. Levin, and T. W. Randolph. Effects of tween 80 and sucrose on acute short–term stability and long–term storage at–20 degrees C of a recombinant hemoglobin. J. Pharm. Sci. 87:1062–1068 (1998).Google Scholar
  60. 60.
    S. D. Webb, J. L. Cleland, J. F. Carpenter, and T. W. Randolph. A new mechanism for decreasing aggregation of recombinant human interferon–gamma by a surfactant: Slowed dissolution of lyophilized formulations in a solution containing 0.03% polysorbate 20. J. Pharm. Sci. 91:543–558 (2002).Google Scholar
  61. 61.
    B. S. Kendrick, J. F. Carpenter, J. L. Cleland, and T. W. Randolph. A transient expansion of the native state precedes aggregation of recombinant human interferon–γ. Proc. Natl. Acad. Sci. USA 95:14142–14146 (1998).Google Scholar
  62. 62.
    B. L. Chen and T. Arakawa. Stabilization of recombinant human keratinocyte growth factor by osmolytes and salts. J. Pharm. Sci. 85:419–422 (1996).Google Scholar
  63. 63.
    B. S. Kendrick, B. S. Chang, T. Arakawa, B. Peterson, T. W. Randolph, M. C. Manning, and J. F. 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).Google Scholar
  64. 64.
    T. Arakawa and S. N. Timasheff. Mechanism of protein salting in and salting out by divalent–cation salts — balance between hydration and salt binding. Biochemistry 23:5912–5923 (1984).Google Scholar
  65. 65.
    D. S. MacLean, Q. S. Qian, and C. R. Middaugh. Stabilization of proteins by low molecular weight multi–ions. J. Pharm. Sci. 91:2220–2229 (2002).Google Scholar
  66. 66.
    C. Nishimura, V. N. Uversky, and A. L. Fink. Effect of salts on the stability and folding of staphylococcal nuclease. Biochem. 40:2113–2128 (2001).Google Scholar
  67. 67.
    R. A. Curtis, J. Ulrich, A. Montaser, J. M. Prausnitz, and H. W. Blanch. Protein–protein interactions in concentrated electrolyte solutions — hofmeister–series effects. Biotechnol. Bioeng. 79:367–380 (2002).Google Scholar
  68. 68.
    M. Yamasaki, H. Yano, and K. Aoki. Differential scanning calorimetric studies on bovine serum–albumin.2. Effects of neutral salts and urea. Int. J. Biol. Macromol. 13:322–328 (1991).Google Scholar
  69. 69.
    B. L. Chen, X. R. Wu, S. J. Babuka, and M. Hora. Solubility of recombinant human tissue factor pathway inhibitor. J. Pharm. Sci. 88:881–888 (1999).Google Scholar
  70. 70.
    M. Z. Zhang, J. Wen, T. Arakawa, and S. J. Prestrelski. A new strategy for enhancing the stability of lyophilized protein — the effect of the reconstitution medium on keratinocyte growth–factor. Pharm. Res. 12:1447–1452 (1995).Google Scholar
  71. 71.
    T. Arakawa. Hydration as a major factor in preferential solvent–protein interactions. Cryst. Growth Des. 2:549–551 (2002).Google Scholar
  72. 72.
    R. L. Remmele, N. S. Nightlinger, S. Srinivasan, and W. R. Gombotz. Interleukin–1 receptor (IL–1R) liquid formulation development using differential scanning calorimetry. Pharm. Res. 15:200–208 (1998).Google Scholar
  73. 73.
    J. Fransson, D. Hallen, and E. FlorinRobertsson. Solvent effects on the solubility and physical stability of human insulin–like growth factor I. Pharm. Res. 14:606–612 (1997).Google Scholar
  74. 74.
    X. M. Lam, T. W. Patapoff, and T. H. Nguyen. The effect of benzyl alcohol on recombinant human interferon–gamma. Pharm. Res. 14:725–729 (1997).Google Scholar
  75. 75.
    L. S. Jones, N. B. Bam, and T. W. Randolph. Surfactant–stabilized protein formulations: A review of protein–surfactants interactions and novel analytical methodologies. In Z. Shahrokhs (ed.), Therapeutic Protein and Peptide Formulation and Delivery, American Chemical Society, Washington, DC, 1997, pp. 206–222.Google Scholar
  76. 76.
    N. B. Bam, J. L. Cleland, J. Yang, M. C. Manning, J. F. Carpenter, R. F. Kelley, and T. W. Randolph. Tween protects recombinant human growth hormone against agitation–induced damage via hydrophobic interactions. J. Pharm. Sci. 87:1554–1559 (1998).Google Scholar
  77. 77.
    N. B. Bam, J. L. Cleland, and T. W. Randolph. Molten globule intermediate of recombinant human growth hormone: Stabilization with surfactants. Biotechnol. Prog. 12:801–809 (1996).Google Scholar
  78. 78.
    M. N. Jones. Protein–surfactant interactions. In S. Magdassis (eds.), Surface Activity of Proteins: Chemical and Physicochemical Modifications, Marcel Dekker, New York, 1996, p. 327.Google Scholar
  79. 79.
    A. L. Fink, L. J. Calciano, Y. Goto, T. Kurotsu, and D. R. Palleros. Classification of acid denaturation of proteins–intermediates and unfolded states. Biochemistry 33:12504–12511 (1994).Google Scholar
  80. 80.
    R. Carrotta, R. Bauer, R. Waninge, and C. Rischel. Conformational characterization of oligomeric intermediates and aggregates in beta–lactoglobulin heat aggregation. Protein Sci. 10:1312–1318 (2001).Google Scholar
  81. 81.
    I. Gomez–Orellana, B. Variano, J. Miura–Fraboni, S. Milstein, and D. R. Paton. Thermodynamic characterization of an intermediate state of human growth hormone. Protein Sci. 7:1352–1358 (1998).Google Scholar
  82. 82.
    M. A. Speed, T. Morshead, and D. I. C. Wang. and J. King. Conformation of p22 tailspike folding and aggregation intermediates probed by monoclonal antibodies. Protein Sci. 6:99–108 (1997).Google Scholar
  83. 83.
    J. King, C. HaasePettingell, A. S. Robinson, M. Speed, and A. Mitraki. Thermolabile folding intermediates: Inclusion body precursors and chaperonin substrates. FASEB J. 10:57–66 (1996).Google Scholar
  84. 84.
    D. Y. Kim and M. H. Yu. Folding pathway of human alpha(1)–antitrypsin: Characterization of an intermediate that is active but prone to aggregation. Biochem. Biophys. Res. Commun. 226:378–384 (1996).Google Scholar
  85. 85.
    R. Khurana, J. R. Gillespie, A. Talapatra, L. J. Minert, C. Ionescu–Zanetti, I. Millett, and A. L. Fink. Partially folded intermediates as critical precursors of light chain amyloid fibrils and amorphous aggregates. Biochemistry 40:3525–3535 (2001).Google Scholar
  86. 86.
    A. O. Grillo, K. L. T. Edwards, R. S. Kashi, K. M. Shipley, L. Hu, M. J. Besman, and C. R. Middaugh. Conformational origin of the aggregation of recombinant human factor VIII. Biochemistry 40:586–595 (2001).Google Scholar
  87. 87.
    J. N. Webb, S. D. Webb, J. L. Cleland, J. F. Carpenter, and T. W. Randolph. Partial molar volume, surface area, hydration changes for equilibrium unfolding and formation of aggregation transition state: High–pressure and cosolute studies on recombinant human ifn–γ. Proc. Natl. Acad. Sci. USA 98:7259–7264 (2001).Google Scholar
  88. 88.
    J. M. Friedman. Time–resolved resonance raman–spectroscopy as probe of structure, dynamics, and reactivity in hemoglobin. Methods Enzymol. 232:205–231 (1994).Google Scholar
  89. 89.
    A. D. Barksdale, D. G. Knox, and A. Rosenberg. Structure dynamics of proteins by hydrogen–exchange methods. Biophys. J. 32:619–621 (1980).Google Scholar
  90. 90.
    J. M. Sanchez–Ruiz. Theoretical analysis of Lumry–Eyring models in differential scanning calorimetry. Biophy. J. 61:921–935 (1992).Google Scholar
  91. 91.
    S. E. Zale and A. M. Klibanov. On the role of reversible denaturation (unfolding) in the irreversible thermal inactivation of enzymes. Biotechnol. Bioeng. 25:2221–2230 (1983).Google Scholar
  92. 92.
    S. N. Timasheff and T. Arakawa. Mechanism of protein precipitation and stabilization by co–solvents. J. Cryst. Growth 90:39–46 (1988).Google Scholar
  93. 93.
    A. George, Y. Chiang, B. Guo, A. Arabshahi, Z. Cai, and W. W. Wilson. Second virial coefficient as predictor in protein crystal growth. Methods Enzymol. 276:100–110 (1997).Google Scholar
  94. 94.
    D. Rosenbaum, P. C. Zamora, and C. F. Zukoski. Phase behavior of small attractive colloidal particles. Phys. Rev. Lett. 76:150–153 (1996).Google Scholar
  95. 95.
    C. Haas and J. Drenth. Understanding protein crystallization on the basis of the phase diagram. J. Cryst. Growth 196:388–394 (1999).Google Scholar
  96. 96.
    R. A. Curtis, H. W. Blanch, and J. M. Prausnitz. Calculation of phase diagrams for aqueous protein solutions. J. Phys. Chem. B 105:2445–2452 (2001).Google Scholar
  97. 97.
    M. Farnum and C. Zukoski. Effect of glycerol on the interactions and solubility of bovine pancreatic trypsin inhibitor. Biophys. J. 76:2716–2726 (1999).Google Scholar
  98. 98.
    B. Guo, S. Kao, H. McDonald, A. Asanov, L. L. Combs, and W. W. Wilson. Correlation of second virial coefficients and solubilities useful in protein crystal growth. J. Cryst. Growth 196:424–433 (1999).Google Scholar
  99. 99.
    C. Haas, J. Drenth, and W. W. Wilson. Relation between the solubility of proteins in aqueous solutions and the second virial coefficient of the solution. J. Phys. Chem. B 103:2808–2811 (1999).Google Scholar
  100. 100.
    D. F. Rosenbaum and C. F. Zukoski. Protein interactions and crystallization. J. Cryst. Growth 169:752–758 (1996).Google Scholar
  101. 101.
    A. George and W. W. Wilson. Predicting protein crystallization from a dilute solution property. Acta Cryst. D50:361–365 (1994).Google Scholar
  102. 102.
    P. E. Pjura, A. M. Lenhoff, S. A. Leonard, and A. G. Gittis. Protein crystallization by desigh: Chymotrypsinogen without precipitants. J. Mol. Biol. 300:235–239 (2000).Google Scholar
  103. 103.
    O. D. Velev, E. W. Kaler, and A. M. Lenhoff. Protein interactions in solution characterized by light and neutron scattering: Comparison of lysozyme and chymotrypsinogen. Biophys. J. 75:2682–2697 (1998).Google Scholar
  104. 104.
    S. Krishnan, E. Y. Chi, S. J. Wood, B. S. Kendrick, C. Li, W. Garzon–Rodriguez, J. Wypych, T. W. Randolph, L. O. Narhi, A. L. Biere, M. Citron, and J. F. Carpenter. Oxidative dimer formation is the critical rate–limiting step for Parkinson's disease α–synuclein fibrillogenesis. Biochemistry 42:829–837 (2002).Google Scholar
  105. 105.
    D. Hamada and C. M. Dobson. A kinetic study of beta–lactoglobulin amyloid fibril formation promoted by urea. Protein Sci. 11:2417–2426 (2002).Google Scholar
  106. 106.
    J. H. Come, P. E. Fraser, and P. T. Lansbury. A kinetic–model for amyloid formation in the prion diseases — importance of seeding. Proc. Natl. Acad. Sci. USA 90:5959–5963 (1993).Google Scholar
  107. 107.
    J. Zurdo, J. I. Guijarro, J. L. Jimenez, H. R. Saibil, and C. M. Dobson. Dependence on solution conditions of aggregation and amyloid formation by an sh3 domain. J. Mol. Biol. 311:325–340 (2001).Google Scholar
  108. 108.
    S. M. Chen, V. Berthelier, J. B. Hamilton, B. O'Nuallain, and R. Wetzel. Amyloid–like features of polyglutamine aggregates and their assembly kinetics. Biochem. 41:7391–7399 (2002).Google Scholar
  109. 109.
    P. G. Debenedetti. Metastable Liquids: Concepts and Principles, Princeton University Press, Princeton, 1996.Google Scholar
  110. 110.
    A. D. Randolph and M. A. Larson. Theory of Particulate Processes: Analysis and Techniques of Continuous Crystallization, Academic Press Inc., San Diego, California, 1988.Google Scholar
  111. 111.
    H. Naiki and F. Gejyo. Kinetic analysis of amyloid fibril formation. Methods Enzymol. 309:305–318 (1999).Google Scholar

Copyright information

© Plenum Publishing Corporation 2003

Authors and Affiliations

  • Eva Y. Chi
    • 1
  • Sampathkumar Krishnan
    • 2
  • Theodore W. Randolph
    • 1
  • John F. Carpenter
    • 3
  1. 1.Department of Chemical Engineering, Center for Pharmaceutical Biotechnology, ECCH 111University of ColoradoBoulder
  2. 2.Department of Pharmaceutics and Drug DeliveryAmgen Inc.Thousand Oaks
  3. 3.Department of Pharmaceutical Sciences, School of PharmacyUniversity of Colorado Health Sciences CenterDenver

Personalised recommendations