Applying Promiscuous RiPP Enzymes to Peptide Backbone N-Methylation Chemistry.

ABSTRACT: The methylation of peptide backbone amides is a hallmark of bioactive natural products, and it also greatly modifies the pharmacology of synthetic peptides. Usually, bioactive N-methylated peptides are cyclic. However, there is very limited knowledge about how post-translational enzymes can be applied to the synthesis of designed N-methylated peptides or peptide libraries. Here, driven by the established ability of some RiPP enzymes to process diverse substrates, we sought to define catalysts for the in vivo and in vitro macrocyclization of backbone-methylated peptides. We developed efficient methods in which short, synthetic N-methylated peptides could be modified using side chain and mainchain macrocyclases, PsnB and PCY1 from plesiocin and orbitide bio

SUBMITTER: Sarkar S 

PROVIDER: S-EPMC9526446 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature