Orthogonal Methods for Characterizing the Unfolding of Therapeutic Monoclonal Antibodies: Differential Scanning Calorimetry, Isothermal Chemical Denaturation, and Intrinsic Fluorescence with Concomitant Static Light Scattering

Methods in Enzymology
Deniz B TemelMark L Brader

Abstract

Evaluating prospective protein pharmaceutical stability from accelerated screening is a critical challenge in biotherapeutic discovery and development. Measurements of protein unfolding transitions are widely employed for comparing candidate molecules and formulations; however, the interrelationships between intrinsic protein conformational stability and pharmaceutical robustness are complex and thermal unfolding measurements can be misleading. Beyond the discovery phase of drug development, astute formulation design is one of the most crucial factors enabling the protein to resist damage to its higher order structure-initially from bioprocessing stresses, then from stresses encountered during its journey from the product manufacturing site to the bloodstream of the patient. Therapeutic monoclonal antibodies are multidomain proteins that represent a large and growing segment of the biotechnology pipeline. In this chapter, we describe how differential scanning calorimetry may be leveraged synergistically with isothermal chemical denaturation and intrinsic fluorescence with concomitant static light scattering to elucidate characteristics of mAb unfolding and aggregation that are helpful toward understanding and designing optimal ...Continue Reading

Citations

Apr 4, 2017·Protein Science : a Publication of the Protein Society·Gabriel ŽoldákErik Sedlák
Mar 15, 2018·MAbs·Jonas V SchaeferAndreas Plückthun
Jun 13, 2017·Chembiochem : a European Journal of Chemical Biology·Katharina VeithHenning Tidow
Mar 21, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·John T BarrLarry C Wienkers
Sep 8, 2017·Scientific Reports·Fabian RiesFelix Willmund
Aug 24, 2017·Protein Science : a Publication of the Protein Society·Michal NemergutErik Sedlák
Jun 20, 2018·Nature Nanotechnology·Manuel TonigoldVolker Mailänder
Apr 23, 2021·Journal of the American Society for Mass Spectrometry·Iain D G Campuzano, Wendy Sandoval
Aug 25, 2018·Molecular Pharmaceutics·Jacob B RoweYing Wang
Oct 31, 2019·Biochemistry·María Georgina HerreraJavier Santos
Nov 20, 2019·The Journal of Physical Chemistry. B·Glenn M FerreiraChristopher J Roberts
Nov 15, 2017·The Journal of Physical Chemistry. B·Alexander B KuhnLars V Schäfer
Nov 10, 2020·The Journal of Physical Chemistry. a·Gonzalo Díaz Mirón, Mariano C González Lebrero

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.