Localized conformational interrogation of antibody and antibody-drug conjugates by site-specific carboxyl group footprinting.

ABSTRACT: Establishing and maintaining conformational integrity of monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) during development and manufacturing is critical for ensuring their clinical efficacy. As presented here, we applied site-specific carboxyl group footprinting (CGF) for localized conformational interrogation of mAbs. The approach relies on covalent labeling that introduces glycine ethyl ester tags onto solvent-accessible side chains of protein carboxylates. Peptide mapping is used to monitor the labeling kinetics of carboxyl residues and the labeling kinetics reflects the conformation or solvent-accessibility of side chains. Our results for two case studies are shown here. The first study was aimed at defining the conformational changes of mAbs induced by deglycosylatio

SUBMITTER: Pan LY 

PROVIDER: S-EPMC5297533 | biostudies-literature | 2017 Feb/Mar

REPOSITORIES: biostudies-literature