Rational design of new cyclic analogues of the antimicrobial lipopeptide tridecaptin A

Non-ribosomal peptides (NRPs) are a rich source of antibiotic candidates. However, it was recently discovered that resistance to NRPs can be mediated by d -stereoselective peptidases. The tridecaptins, a class of NRPs that selectively target Gram-negative bacteria, are degraded by the d -peptidase T...

Full description

Saved in:
Bibliographic Details
Published in:Chemical communications (Cambridge, England) England), 2018-09, Vol.54 (75), p.1634-1637
Main Authors: Ballantine, Ross D, Li, Yong-Xin, Qian, Pei-Yuan, Cochrane, Stephen A
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Non-ribosomal peptides (NRPs) are a rich source of antibiotic candidates. However, it was recently discovered that resistance to NRPs can be mediated by d -stereoselective peptidases. The tridecaptins, a class of NRPs that selectively target Gram-negative bacteria, are degraded by the d -peptidase TriF. Through analysis of a solution NMR structure of tridecaptin A 1 , we have rationally synthesized new cyclic tridecaptin analogues that retain strong antimicrobial activity and are resistant to TriF. Cyclization of tridecaptin A 1 imparts stability to the d -peptidase TriF.
ISSN:1359-7345
1364-548X
DOI:10.1039/c8cc05790g