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

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

doi:10.1021/acs.jmedchem.9b01078

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

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

School of Chemistry and Chemical Engineering

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

95 Downloads (Pure)

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 language	English
Pages (from-to)	10466-10472
Journal	Journal of Medicinal Chemistry
Volume	62
Issue number	22
DOIs	https://doi.org/10.1021/acs.jmedchem.9b01078
Publication status	Published - 27 Nov 2019

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10.1021/acs.jmedchem.9b01078Licence: CC BY

A Chemical-Intervention Strategy To Circumvent Peptide Hydrolysis by d-Stereoselective Peptidases
Copyright 2019 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 909 KBLicence: CC BY

Structural and mechanistic studies on antimicrobial peptides that target multi-drug resistant bacteria
Author: Ballantine, R., Jul 2021
Supervisor: Cochrane, S. (Supervisor) & Stevenson, P. (Supervisor)
Student thesis: Doctoral Thesis › Doctor of Philosophy

Cite this

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AU - Cochrane, Stephen

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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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JF - Journal of Medicinal Chemistry

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

Abstract

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Student Theses

Structural and mechanistic studies on antimicrobial peptides that target multi-drug resistant bacteria

Cite this