A Chemical-Intervention Strategy to Circumvent Peptide Hydrolysis by D-Stereoselective Peptidases

Samantha Bann, Ross Ballantine, Yong-Xin Li, Pei-Yuan Qian, Stephen Cochrane

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Abstract

D-Stereoselective peptidases that degrade non-ribosomal peptides (NRPs) were recently discovered and could have serious implications for the future of NRPs as antibiotics. Herein, we report chemical modifications that can be used to impart re-sistance to the D-peptidases BogQ and TriF. New tridecaptin A analogues were synthesized that retain strong antimicrobial activity and have significantly enhanced D-peptidase stability. In vitro assays confirmed that synthetic analogues retain the ability to bind to their cellular receptor, peptidoglycan intermediate lipid II.
Original languageEnglish
Pages (from-to)10466-10472
JournalJournal of Medicinal Chemistry
Volume62
Issue number22
DOIs
Publication statusPublished - 27 Nov 2019

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