Reversibility and irreversibility in the temperature denaturation of monoclonal antibodies.

Analytical Biochemistry
Arne Schön, Ernesto Freire

Abstract

There have been numerous studies of the temperature denaturation of monoclonal antibodies (mAbs) using differential scanning calorimetry (DSC). In general, mAbs are characterized by complex temperature denaturation transitions in which the various domains (CH2, CH3, Fab) give rise to different peaks in the heat capacity function. The complexity and overall irreversibility of the temperature denaturation transition is well known and has limited the number of publications with an in-depth analysis of the data. Here we report that the temperature denaturation of the CH2 domain is reversible and only becomes irreversible after denaturation of the Fab domain, which is intrinsically irreversible. For these studies we have used the HIV neutralizing monoclonal antibody 17b. To account for the experimental heat capacity function, a mixed denaturation model that combines multiple reversible and irreversible transitions has been developed. This model accounts well for the DSC data and for the pH dependence of the heat capacity function of 17b and other monoclonal antibodies for which data is available in the literature. It is expected that a more detailed analysis of the stability of monoclonal antibodies will contribute to the developmen...Continue Reading

References

Jan 1, 1979·Advances in Protein Chemistry·P L Privalov
Jan 1, 1995·Methods in Enzymology·E Freire
May 17, 2001·Proceedings of the National Academy of Sciences of the United States of America·M JaminR L Baldwin
Aug 5, 1997·Chemical Reviews·Andrew D. Robertson, Kenneth P. Murphy
Mar 16, 2005·Proceedings of the National Academy of Sciences of the United States of America·Steven T WhittenVincent J Hilser
Feb 27, 2007·Biochemical and Biophysical Research Communications·Ellen Garber, Stephen J Demarest
Aug 28, 2007·Journal of Pharmaceutical Sciences·Roxana M IonescuMarc Kirchmeier
Aug 22, 2013·Protein Science : a Publication of the Protein Society·Takahiko Ito, Kouhei Tsumoto
May 12, 2018·Analytical Biochemistry·Benjamin R ClarksonErnesto Freire
Jul 19, 2018·Journal of Pharmaceutical Sciences·Harumi FukadaDaisuke Ejima
Apr 24, 2020·Computational and Structural Biotechnology Journal·Max HebditchJim Warwicker

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.