Rapid Peptide Cyclization Inspired by the Modular Logic of Nonribosomal Peptide Synthetases.

ABSTRACT: Nonribosomal cyclic peptides (NRcPs) are structurally complex natural products and a vital pool of therapeutics, particularly antibiotics. Their structural diversity arises from the ability of the multidomain enzyme assembly lines, nonribosomal peptide synthetases (NRPSs), to utilize bespoke nonproteinogenic amino acids, modify the linear peptide during elongation, and catalyze an array of cyclization modes, e.g., head to tail, side chain to tail. The study and drug development of NRcPs are often limited by a lack of easy synthetic access to NRcPs and their analogues, with selective macrolactamization being a major bottleneck. Herein, we report a generally applicable chemical macrocyclization method of unprecedented speed and selectivity. Inspired by biosynthetic cyclization, it combines t

SUBMITTER: Ding Y 

PROVIDER: S-EPMC11191687 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature