Extrapolating differential scanning calorimetry data for monoclonal antibodies to low temperatures.

Autor: Schön A; Department of Biology, Johns Hopkins University, 3400 North Charles, Baltimore, MD, 21218, USA., Kwon YD; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA., Bender MF; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA., Freire E; Department of Biology, Johns Hopkins University, 3400 North Charles, Baltimore, MD, 21218, USA. Electronic address: ef@jhu.edu.
Jazyk: angličtina
Zdroj: Analytical biochemistry [Anal Biochem] 2024 Aug; Vol. 691, pp. 115533. Date of Electronic Publication: 2024 Apr 19.
DOI: 10.1016/j.ab.2024.115533
Abstrakt: For irreversible denaturation transitions such as those exhibited by monoclonal antibodies, differential scanning calorimetry provides the denaturation temperature, T m , the rate of denaturation at T m , and the activation energy at T m . These three quantities are essential but not sufficient for an accurate extrapolation of the rate of denaturation to temperatures of 25 °C and below. We have observed that the activation energy is not constant but temperature dependent due to the existence of an activation heat capacity, C p,a . It is shown in this paper that a model that incorporates C p,a is able to account for previous observations like, for example, that increasing the T m does not always improve the stability at low temperatures; that some antibodies exhibit lower stabilities at 5 °C than at 25 °C; or that low temperature stabilities do not follow the rank order derived from T m values. Most importantly, the activation heat capacity model is able to reproduce time dependent stabilities measured by size exclusion chromatography at low temperatures.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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