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Chemical Synthesis of a Potent Antimicrobial Peptide Murepavadin Using a Tandem Native Chemical Ligation/Desulfurization Reaction.

ABSTRACT: Classical approaches for the backbone cyclization of polypeptides require conditions that may compromise the chirality of the C-terminal residue during the activation step of the cyclization reaction. Here, we describe an efficient epimerization-free approach for the Fmoc-based synthesis of murepavadin using intramolecular native chemical ligation in combination with a concomitant desulfurization reaction. Using this approach, bioactive murepavadin was produced in a good yield in two steps. The synthetic peptide antibiotic showed potent activity against different clinical isolates of P. aeruginosa. This approach can be easily adapted for the production of murepavadin analogues and other backbone-cyclized peptides.

SUBMITTER: Chaudhuri D

PROVIDER: S-EPMC8935662 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Chemical Synthesis of a Potent Antimicrobial Peptide Murepavadin Using a Tandem Native Chemical Ligation/Desulfurization Reaction.

Chaudhuri Dipankar D Ganesan Rajasekaran R Vogelaar Alicia A Dughbaj Mansour A MA Beringer Paul M PM Camarero Julio A JA

The Journal of organic chemistry 20211012 21

Classical approaches for the backbone cyclization of polypeptides require conditions that may compromise the chirality of the C-terminal residue during the activation step of the cyclization reaction. Here, we describe an efficient epimerization-free approach for the Fmoc-based synthesis of murepavadin using intramolecular native chemical ligation in combination with a concomitant desulfurization reaction. Using this approach, bioactive murepavadin was produced in a good yield in two steps. The ...[more]

PMID: 34641669

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