Synthesis and Structure–Activity Relationship Studies of N‑Terminal Analogues of the Antimicrobial Peptide Tridecaptin A1

Chemical synthesis was used to increase the potency of the antimicrobial lipopeptide tridecaptin A1. Lipid tail modification proved to be an ideal platform for synthesizing structurally simpler analogues that are not readily accessible by isolation. The stereochemical elements of the tridecaptin A1...

Full description

Saved in:
Bibliographic Details
Published in:Journal of medicinal chemistry 2014-02, Vol.57 (3), p.1127-1131
Main Authors: Cochrane, Stephen A, Lohans, Christopher T, Brandelli, Jeremy R, Mulvey, George, Armstrong, Glen D, Vederas, John C
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Chemical synthesis was used to increase the potency of the antimicrobial lipopeptide tridecaptin A1. Lipid tail modification proved to be an ideal platform for synthesizing structurally simpler analogues that are not readily accessible by isolation. The stereochemical elements of the tridecaptin A1 lipid tail are not essential for antimicrobial activity and could be replaced with hydrophobic aliphatic or aromatic groups. Some simpler analogues displayed potent antimicrobial activity against Gram-negative bacteria, including Campylobacter jejuni, Escherichia coli O157:H7, and multidrug resistant Klebsiella pneumoniae.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm401779d