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

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

Research output: Contribution to journalArticle

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.
LanguageEnglish
JournalJournal of Medicinal Chemistry
DOIs
Publication statusAccepted - 28 Oct 2019

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proline dipeptidase
Hydrolysis
Peptides
Anti-Bacterial Agents

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title = "A Chemical-Intervention Strategy to Circumvent Peptide Hydrolysis by D-Stereoselective Peptidases",
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.",
author = "Samantha Bann and Ross Ballantine and Yong-Xin Li and Pei-Yuan Qian and Stephen Cochrane",
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AU - Ballantine, Ross

AU - Li, Yong-Xin

AU - Qian, Pei-Yuan

AU - Cochrane, Stephen

PY - 2019/10/28

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AB - 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.

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DO - 10.1021/acs.jmedchem.9b01078

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