Introducing CLipPA lipid chemodiversity to enzymatically truncated polymyxin B: a soft drug strategy to combat Gram-negative pathogens.

ABSTRACT: A chemodiverse library of new semi-synthetic antimicrobial peptides is reported herein. The polymyxin B nonapeptide (PMBN) holds promise as a developmental platform to access potent antimicrobial lipopeptide derivatives that circumvent the serious side effects of natural polymyxins used in clinical settings. By combining our unique radical thiol-ene lipidation strategy (CLipPA) with a chemoenzymatic synthesis, we achieved the chemoselective re-functionalisation of semi-synthetic PMBN, affording a family of potent "soft drugs" decorated with linear, cyclo- and branched alkyl and aromatic esters of varying steric properties. The high efficiency of this late-stage diversification strategy is demonstrated for lipopeptide semi-synthesis. In this process, the significance of the lipid orientatio

SUBMITTER: Na TU 

PROVIDER: S-EPMC12907753 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature