A Cysteine-Directed Proximity-Driven Crosslinking Method for Native Peptide Bicyclization.

ABSTRACT: Efficient and site-specific modification of native peptides and proteins is desirable for synthesizing antibody-drug conjugates as well as for constructing chemically modified peptide libraries using genetically encoded platforms such as phage display. In particular, there is much interest in efficient multicyclization of native peptides due to the appeals of multicyclic peptides as therapeutics. However, conventional approaches for multicyclic peptide synthesis require orthogonal protecting groups or non-proteinogenic clickable handles. Herein, we report a cysteine-directed proximity-driven strategy for the constructing bicyclic peptides from simple natural peptide precursors. This linear to bicycle transformation initiates with rapid cysteine labeling, which then triggers proximity-drive

SUBMITTER: Chen FJ 

PROVIDER: S-EPMC10527288 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature