Skip to main content
SpringerLink
Log in

Glass Dynamics and the Preservation of Proteins

  • Chapter
Misbehaving Proteins

Abstract

Proteins can be stored, with their biochemical functionality preserved for extended periods under nonphysiological conditions, by enveloping them in certain viscous glass-forming compounds such as trehalose or glycerol. However, the relevant variables that are critical to stabilization are not completely understood, meaning that effective preservation is achieved more often by trial and error than by rational design. While it is widely felt that the viscous preservant must mimic water in terms of thermodynamic interactions with the protein, the precise role of the dynamic interactions between the biomolecule and the preservant still is not clear.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1. M. Bée, Quasielastic Neutron Scattering (Philadelphia, PA: Adam Hilger Press, 1988).

    Google Scholar 

  2. 2. J. S. Higgins and H. C. Benoít, Polymers and Neutron Scattering (Oxford: Carendon Press, 1994).

    Google Scholar 

  3. 3. R. J. Roe, Methods of X-ray and Neutron Scattering in Polymer Science (Oxford: University Press, Oxford, 2000).

    Google Scholar 

  4. 4. J. F. Carpenter, L. M. Crowe, and J. H. Crowe, Stabilization of phosphofructokinase with sugars during freeze-drying: characterization of enhanced protection in the presence of divalent cations, Biochim. Biophys. Acta 923, 109–115 (1987).

    PubMed  CAS  Google Scholar 

  5. 5. R. Mouradian, C. Womersley, L. M. Crowe, and J. H. Crowe, Preservation of functional integrity during long term storage of a biological membrane, Biochim. Biophys. Acta 778, 615–617 (1984).

    Article  PubMed  CAS  Google Scholar 

  6. 6. C. M. Henery, The next pharmaceutical century, Chem. Eng. News 78, 85–100 (2000).

    Google Scholar 

  7. 7. S. D. Allison, B. Chang, T. W. Randolph, and J. F. Carpenter, Hydrogen bonding between sugar and protein is responsible for inhibition of dehydration-induced protein unfolding, Arch. Biochem. Biophys. 365, 289–298 (1999).

    Article  PubMed  CAS  Google Scholar 

  8. 8. J. L. Cleland, X. Lam, B. Kendrick, J. Yang, T. H. 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, 310–321 (2001).

    Article  PubMed  CAS  Google Scholar 

  9. 9. H. R. Costantino, K. G. Carrasquillo, R. A. Cordero, M. Mumenthaler, C. C. Hsu, and K. Griebenow, Effect of excipients on the stability and structure of lyophilized recombinant human growth hormone, J. Pharm. Sci. 87, 1412–1420 (1998).

    Article  PubMed  CAS  Google Scholar 

  10. 10. K. Tanaka, T. Takeda, and K. Miyajima, Cryoprotective effect of saccharides on denaturation of catalase by freeze-drying, Chem. Pharm. Bull. 39, 1091–1094 (1991).

    CAS  Google Scholar 

  11. 11. K. Izutsu, S. Yoshioka, and T. Terao, Effect of mannitol crystallinity on the stabilization of enzymes during freeze-drying, Chem. Pharm. Bull. (Tokyo) 42, 5–8 (1994).

    CAS  Google Scholar 

  12. 12. M. J. Pikal and D. R. Rigsbee, The stability of insulin in crystalline and amorphous solids: observation of greater stability for the amorphous form, Pharm. Res. 14, 1379–1387 (1997).

    Article  PubMed  CAS  Google Scholar 

  13. 13. A. Ansari, C. M. Jones, E. R. Henry, J. Hofrichter, and W. A. Eaton, The role of solvent viscosity in the dynamics of protein conformational changes, Science 256, 1796–1798 (1992).

    Article  PubMed  CAS  Google Scholar 

  14. 14. D. Beece, L. Eisenstein, H. Frauenfelder, D. Good, M. C. Marden, L. Reinisch, A. H. Reynolds, L. B. Sorensen, and K. T. Yue, Solvent viscosity and protein dynamics, Biochemistry 19, 5147–5157(1980).

    Article  PubMed  CAS  Google Scholar 

  15. 15. W. Doster, Viscosity scaling and protein dynamics, Biophys. Chem. 17, 97–103 (1983).

    Article  PubMed  CAS  Google Scholar 

  16. 16. B. Gavish, Position-dependent viscosity effects on rate coefficients, Phys. Rev. Lett. 44, 1160–1163 (1980).

    Article  CAS  Google Scholar 

  17. 17. T. Kleinert, W. Doster, H. Leyser, W. Petry, V. Schwarz, and M. Settles, Solvent composition and viscosity effects on the kinetics of CO binding to horse myoglobin, Biochemistry 37, 717–733 (1998).

    Article  PubMed  CAS  Google Scholar 

  18. 18. D. S. Gottfried, E. S. Peterson, A. G. Sheikh, J. Q. Wang, M. Yang, and J. M. Friedman, Evidence for damped hemoglobin dynamics in a room temperature trehalose glass, J. Phys. Chem. 100, 12034–12042 (1996).

    Article  CAS  Google Scholar 

  19. 19. S. J. Hagen, J. Hofrichter, and W. A. Eaton, Protein reaction kinetics in a room-temperature glass, Science 269, 959–962 (1995).

    Article  PubMed  CAS  Google Scholar 

  20. 20. H. Lichtenegger, W. Doster, T. Kleinert, A. Birk, B. Sepiol, and G. Vogl, Heme-solvent coupling: a Mossbauer study of myoglobin in sucrose, Biophys. J. 76, 414–422 (1999).

    PubMed  CAS  Google Scholar 

  21. 21. G. M. Sastryand and N. Agmon, Trehalose prevents myoglobin collapse and preserves its internal mobility, Biochemistry 36, 7097–7108 (1997).

    Article  Google Scholar 

  22. 22. J. Schlichter, J. Friedrich, L. Herenyi, and J. Fidy, Trehalose effect on low temperature protein dynamics: fluctuation and relaxation phenomena, Biophys. J. 80, 2011–2017 (2001).

    PubMed  CAS  Google Scholar 

  23. 23. J. L. Green and C. A. Angell, Phase-relations and vitrification in saccharide-water solutions and the trehalose anomaly, J. Phys. Chem. 93, 2880–2882 (1989).

    Article  CAS  Google Scholar 

  24. 24. L. N. Bell, M. J. Hageman, and L. M. Muraoka, Thermally induced denaturation of lyophilized bovine somatotropin and lysozyme as impacted by moisture and excipients, J. Pharm. Sci. 84, 707–712 (1995).

    Article  PubMed  CAS  Google Scholar 

  25. 25. J. Buitink, I. J. van den Dries, F. A. Hoekstra, M. Alberda, and M. A. Hemminga, High critical temperature above Tg may contribute to the stability of biological systems, Biophys. J. 79, 1119–1128 (2000).

    Article  PubMed  CAS  Google Scholar 

  26. 26. S. P. Duddu, G. Zhang, and P. R. Dal Monte, The relationship between protein aggregation and molecular mobility below the glass transition temperature of lyophilized formulations containing a monoclonal antibody, Pharm. Res. 14, 596–600 (1997).

    Article  PubMed  CAS  Google Scholar 

  27. 27. W. Wang, Lyophilization and development of solid protein pharmaceuticals, Int. J. Pharm. 203, 1–60 (2000).

    Article  PubMed  CAS  Google Scholar 

  28. 28. M. P. Buera, S. Rossi, S. Moreno, and J. Chirife, DSC confirmation that vitrification is not necessary for stabilization of the restriction enzyme EcoRI dried with saccharides, Biotechnol. Prog. 15, 577–579 (1999).

    Article  PubMed  CAS  Google Scholar 

  29. 29. P. Davidson and W. Q. Sun, Effect of sucrose/raffinose mass ratios on the stability of co-lyophilized protein during storage above the Tg, Pharm. Res. 18, 474–479 (2001).

    Article  PubMed  CAS  Google Scholar 

  30. 30. M. T. Cicerone, A. Tellington, L. Trost, and A. P. Sokolov, Substantially Improved stability of biological agents in dried form, BioProcess Int. 1, 36–47 (2003).

    CAS  Google Scholar 

  31. 31. M. T. Cicerone and C. L. Soles, Fast dynamics and stabilization of proteins: binary glasses of trehalose and glycerol, Biophys. J. 86, 3836–3845 (2004).

    Article  PubMed  CAS  Google Scholar 

  32. 32. P. M. Gehring and D. A. Neumann, Backscattering spectroscopy at the NIST Center for Neutron Research, Physica B 241, 64–70 (1997).

    Article  Google Scholar 

  33. 33. B. Frick, and L. J. Fetters, Methyl-group dynamics in glassy polyisoprene—A neutron backscattering investigation, Macromolecules 27, 974–980 (1994).

    Article  CAS  Google Scholar 

  34. 34. A. Paciaroni, S. Cinelli, and G. Onori, Effect of the environment on the protein dynamical transition: a neutron scattering study, Biophys J. 83, 1157–1164 (2002).

    PubMed  CAS  Google Scholar 

  35. 35. M. Settles and W. Doster, Anomalous diffusion of adsorbed water: A neutron scattering study of hydrated myoglobin, Farad. Disc. 103, 269–279 (1996).

    Article  CAS  Google Scholar 

  36. 36. G. Zaccaï, How soft is a protein? A protein dynamics force constant measured by neutron scattering, Science 288, 1604–1607 (2000).

    Article  PubMed  Google Scholar 

  37. 37. C. A. Angell, K. L. Ngai, G. B. McKenna, P. F. McMillan, and S. W. Martin, Relaxation in glass-forming liquids and amorphous solids, J. Appl. Phys. 88, 3113–3157 (2000).

    Article  CAS  Google Scholar 

  38. 38. B. Frick and D. Richter, The microscopic basis of the glass-transition in polymers from neutron-scattering studies, Science 267, 1939–1945 (1995).

    Article  PubMed  CAS  Google Scholar 

  39. 39. P. B. Conrad and J. J. de Pablo, Computer simulation of the cryoprotectant disaccharide alpha, alpha-trehalose in aqueous solution, J. Phys. Chem. A 103, 4049–4055 (1999).

    Article  CAS  Google Scholar 

  40. 40. V. K. Malinovsky, V. N. Novikov, and A. P. Sokolov, Log-normal spectrum of low-energy vibrational excitations in glasses, Phys. Lett. A 153, 63–66 (1991).

    Article  Google Scholar 

  41. 41. U. Buchenau, Y. M. Galperin, V. L. Gurevich, and H. R. Schober, Anharmonic potentials and vibrational localization in glasses, Phys. Rev. B 43, 5039–5045 (1991).

    Article  Google Scholar 

  42. 42. O. Yamamuro, K. Harabe, T. Matsuo, K. Takeda, I. Tsukushi, and T. Kanaya, Boson peaks of glassy mono- and polyalcohols studied by inelastic neutron scattering, J. Phys. Conden. Matt. 12, 5143–5154 (2000).

    Article  CAS  Google Scholar 

  43. 43. A. P. Sokolov, A. Kisliuk, D. Quitmann, A. Kudlik, and E. Rossler, The dynamics of strong and fragile glass formers—vibrational and relaxation contributions, J. Non-Cryst. Solids 172, 138–153 (1994).

    Article  Google Scholar 

  44. 44. D. Lourdin, H. Bizot, and P. Colonna, Correlation between static mechanical properties of starch-glycerol materials and low-temperature relaxation, Macromol. Symp. 114, 179–185 (1997).

    CAS  Google Scholar 

  45. 45. T. R. Noel, R. Parker, and S. G. Ring, A comparative study of the dielectric relaxation behaviour of glucose, maltose, and their mixtures with water in the liquid and glassy states, Carb. Res. 282, 193–206 (1996).

    Article  CAS  Google Scholar 

  46. 46. P. Bergquist, Y. Zhu, A. A. Jones, and P. T. Inglefield, Plasticization and antiplasticization in polycarbonates: The role of diluent motion, Macromolecules 32, 7925–7931 (1999).

    Article  CAS  Google Scholar 

  47. 47. R. Casalini, K. L. Ngai, C. G. Robertson, and C. M. Roland, Alpha- and beta-relaxations in neat and antiplasticized polybutadiene, J. Poly. Sci. B: Poly. Phys. 38, 1841–1847 (2000).

    Article  CAS  Google Scholar 

  48. 48. R. V. Rariy and A. M. Klibanov, Correct protein folding in glycerol, Proc. Natl. Acad. Sci. USA 94, 13520–13523 (1997).

    Article  PubMed  CAS  Google Scholar 

  49. 49. F. Parak, E. W. Knapp, and D. Kucheida, Protein dynamics—Mossbauer spectroscopy on deoxymyoglobin crystals, J. Mol. Biol. 161, 177–194 (1982).

    Article  PubMed  CAS  Google Scholar 

  50. 50. C. L. Brooks, M. Karplus, and B. M. Pettitt, Proteins: a theoretical perspective of dynamics, structure, and thermodynamics, Adv. Chem. Phys. 1–200 (1988).

    Google Scholar 

  51. 51. W. Doster, S. Cusack, and W. Petry, Dynamical transition of myoglobin revealed by inelastic neutron scattering, Nature 337, 754–756 (1989).

    Article  PubMed  CAS  Google Scholar 

  52. 52. S. Subramaniam, M. Gerstein, D. Oesterhelt, and R. Henderson, Electron diffraction analysis of structural changes in the photocycle of bacteriorhodopsin, EMBO J. 12, 1–8 (1993).

    PubMed  CAS  Google Scholar 

  53. 53. V. Reat, H. Patzelt, M. Ferrand, C. Pfister, D. Oesterhelt, and G. Zaccai, Dynamics of different functional parts of bacteriorhodopsin: H-H-2 labeling and neutron scattering, Proc. Natl. Acad. Sci. USA 95, 4970–4975 (1998).

    Article  PubMed  CAS  Google Scholar 

  54. 54. L. Cordone, M. Ferrand, E. Vitrano, and G. Zaccai, Harmonic behavior of trehalose-coated carbon-monoxy-myoglobin at high temperature, Biophys. J. 76, 1043–1047 (1999).

    PubMed  CAS  Google Scholar 

  55. 55. C. Branca, S. Magazu, G. Maisano, and F. Migliardo, Vibrational and relaxational contributions in disaccharide/H2O glass formers, Phys. Rev. B 64, art-224204 (2001).

    Google Scholar 

  56. 56. G. Caliskan, A. Kisliuk, A. M. Tsai, C. L. Soles, and A. P. Sokolov, Protein dynamics in viscous solvents, J. Chem. Phys. 118, 4230–4236 (2003).

    Article  CAS  Google Scholar 

  57. 57. A. M. Tsai, D. A. Neumann, and L. N. Bell, Molecular dynamics of solid-state lysozyme as affected by glycerol and water: A neutron scattering study, Biophys. J. 79, 2728–2732 (2000).

    PubMed  CAS  Google Scholar 

  58. 58. D. P. Miller and J. J. de Pablo, Calorimetric solution properties of simple saccharides and their significance for the stabilization of biological structure and function, J. Phys. Chem. B 104, 8876–8883 (2000).

    Article  CAS  Google Scholar 

Download references

Authors
  1. Christopher L. Soles
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amos M. Tsai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marcus T. Cicerone
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer

About this chapter

Cite this chapter

Soles, C.L., Tsai, A.M., Cicerone, M.T. (2006). Glass Dynamics and the Preservation of Proteins. In: Misbehaving Proteins. Springer, New York, NY. https://doi.org/10.1007/978-0-387-36063-8_9

Download citation

Publish with us

Policies and ethics

Search

Navigation