Structure-Activity Relationship Studies of the Peptide Antibiotic Clovibactin.

ABSTRACT: Our laboratory reported the chemical synthesis and stereochemical assignment of the recently discovered peptide antibiotic clovibactin. The current paper reports an improved, gram-scale synthesis of the amino acid building block Fmoc-(2R,3R)-3-hydroxyasparagine-OH that enables structure-activity relationship studies of clovibactin. An alanine scan reveals that residues Phe₁, d-Leu₂, Ser₄, Leu₇, and Leu₈ are important for antibiotic activity. The side-chain amide group of the rare d-Hyn₅ residue is not essential to activity and can be replaced with a methyl group with a moderate loss of activity. An acyclic clovibactin analogue reveals that the macrolactone ring is essential to antibiotic activity. The enantiome

SUBMITTER: Brunicardi JEH 

PROVIDER: S-EPMC11382152 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature