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 journal › Article

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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Bann, Samantha ; Ballantine, Ross ; Li, Yong-Xin ; Qian, Pei-Yuan ; Cochrane, Stephen. / A Chemical-Intervention Strategy to Circumvent Peptide Hydrolysis by D-Stereoselective Peptidases. In: Journal of Medicinal Chemistry. 2019.
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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.",
author = "Samantha Bann and Ross Ballantine and Yong-Xin Li and Pei-Yuan Qian and Stephen Cochrane",
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Bann, S, Ballantine, R, Li, Y-X, Qian, P-Y & Cochrane, S 2019, 'A Chemical-Intervention Strategy to Circumvent Peptide Hydrolysis by D-Stereoselective Peptidases', Journal of Medicinal Chemistry. https://doi.org/10.1021/acs.jmedchem.9b01078

A Chemical-Intervention Strategy to Circumvent Peptide Hydrolysis by D-Stereoselective Peptidases. / Bann, Samantha; Ballantine, Ross; Li, Yong-Xin; Qian, Pei-Yuan; Cochrane, Stephen.

In: Journal of Medicinal Chemistry, 28.10.2019.

Research output: Contribution to journal › Article

TY - JOUR

T1 - A Chemical-Intervention Strategy to Circumvent Peptide Hydrolysis by D-Stereoselective Peptidases

AU - Bann, Samantha

AU - Ballantine, Ross

AU - Li, Yong-Xin

AU - Qian, Pei-Yuan

AU - Cochrane, Stephen

PY - 2019/10/28

Y1 - 2019/10/28

N2 - 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.

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.

U2 - 10.1021/acs.jmedchem.9b01078

DO - 10.1021/acs.jmedchem.9b01078

M3 - Article

JO - Journal of Medicinal Chemistry

T2 - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

ER -

Bann S, Ballantine R, Li Y-X, Qian P-Y, Cochrane S. A Chemical-Intervention Strategy to Circumvent Peptide Hydrolysis by D-Stereoselective Peptidases. Journal of Medicinal Chemistry. 2019 Oct 28. https://doi.org/10.1021/acs.jmedchem.9b01078

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