Unfolding and Inactivation

Genetic and Chemical Approaches to the Stabilization of T4 Lysozyme and Human Interferon Gamma against Irreversible Thermal Denaturation
  • Ronald Wetzel
  • L. Jeanne Perry
  • Michael G. Mulkerrin
  • L. Michael Randall
Part of the New Horizons in Therapeutics book series (NHTH)


One of the first criteria used for identifying and classifying proteins was the tendency of these “albuminoid” substances to respond to heating by coagulating in the manner of egg white albumin (see discussion in Fruton, 1972). By the early 1900s, thermally induced coagulation was being studied with purified proteins. By the 1930s, heat- and denaturant-induced coagulation was understood to involve two steps: a heat-dependent denaturation* step associated with an increase in solution viscosity and chemical accessibility of side-chain groups, and a heat-independent, but pH and salt-dependent, aggregation/precipitation step involving newly exposed groups (Wu, 1931; Mirsky and Pauling, 1936; Anson, 1938). A number of these coagulated proteins could be restored to the solubility and other properties of their native states by use of denaturing solvents followed by a return to native conditions (Neurath et al., 1944; Anson, 1945). The early observation of very high temperature coefficients for protein coagulation set this process apart from standard chemical reactions and was compared to the temperature dependence of state changes such as melting (Anson, 1938). Whereas the rates of chemical reactions might increase by a factor of two to three with a 10°C increase in temperature, the rate of coagulation was found to increase by factors of hundreds with a 10°C increase (Chick and Martin, 1912). The developing concepts of the nature of protein structure and stability in the first decades of this century depended greatly on such data.


Disulfide Bond Thermal Inactivation Guanidine Hydrochloride Inactivation Rate Bovine Growth Hormone 
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Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Ronald Wetzel
    • 1
  • L. Jeanne Perry
    • 1
  • Michael G. Mulkerrin
    • 1
  • L. Michael Randall
    • 1
  1. 1.Biomolecular Chemistry DepartmentGenentech, Inc.South San FranciscoUSA

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