A Leader-Guided Substrate Tolerant RiPP Brominase Allows Suzuki-Miyaura Cross-Coupling Reactions for Peptides and Proteins.

ABSTRACT: Bioorthogonal derivatization of peptides and proteins enables investigations into their biological function and allows for exploitation of their therapeutic potential, among other varied deliverables. Herein, we describe a marine halogenating enzyme-assisted bioconjugation strategy in which an N-terminal leader peptide guides bromination of a C-terminal Trp residue in genetically encoded peptides and proteins, setting up further Trp arylation by Suzuki-Miyaura reactions. The bromination and subsequent cross-coupling reactions are residue-specific and regiospecific for the indole-6 position, occur under mild aqueous conditions, and do not require any modification of other Trp residues in the substrate peptide and/or protein. Workflows described herein demonstrate the applicability of halogenating enzymes in bioorthogonal conjugation chemistry.

SUBMITTER: Nguyen NA 

PROVIDER: S-EPMC10286304 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature