Systematic identification of engineered methionines and oxaziridines for efficient, stable, and site-specific antibody bioconjugation.

ABSTRACT: The field of chemical modification of proteins has been dominated by random modification of lysines or more site-specific labeling of cysteines, each with attendant challenges. Recently, we have developed oxaziridine chemistry for highly selective modification of methionine called redox-activated chemical tagging (ReACT) but have not broadly tested the molecular parameters for efficient and stable protein modification. Here we systematically scanned methionines throughout one of the most popular antibody scaffolds, trastuzumab, used for antibody engineering and drug conjugation. We tested the expression, reactivities, and stabilities of 123 single engineered methionines distributed over the surface of the antibody when reacted with oxaziridine. We found uniformly high expression for these

SUBMITTER: Elledge SK 

PROVIDER: S-EPMC7084160 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature