A Chemical-Intervention Strategy To Circumvent Peptide Hydrolysis by d-Stereoselective Peptidases

[Image: see text] d-Stereoselective peptidases that degrade nonribosomal 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 resistance to the d-peptidases BogQ and Tri...

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Autores principales: Bann, Samantha J., Ballantine, Ross D., McCallion, Conor E., Qian, Pei-Yuan, Li, Yong-Xin, Cochrane, Stephen A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2019
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887851/
https://www.ncbi.nlm.nih.gov/pubmed/31657913
http://dx.doi.org/10.1021/acs.jmedchem.9b01078
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author Bann, Samantha J.
Ballantine, Ross D.
McCallion, Conor E.
Qian, Pei-Yuan
Li, Yong-Xin
Cochrane, Stephen A.
author_facet Bann, Samantha J.
Ballantine, Ross D.
McCallion, Conor E.
Qian, Pei-Yuan
Li, Yong-Xin
Cochrane, Stephen A.
author_sort Bann, Samantha J.
collection PubMed
description [Image: see text] d-Stereoselective peptidases that degrade nonribosomal 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 resistance 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. Invitro assays confirmed that synthetic analogues retain the ability to bind to their cellular receptor, peptidoglycan intermediate lipid II.
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spelling pubmed-68878512019-12-05 A Chemical-Intervention Strategy To Circumvent Peptide Hydrolysis by d-Stereoselective Peptidases Bann, Samantha J. Ballantine, Ross D. McCallion, Conor E. Qian, Pei-Yuan Li, Yong-Xin Cochrane, Stephen A. J Med Chem [Image: see text] d-Stereoselective peptidases that degrade nonribosomal 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 resistance 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. Invitro assays confirmed that synthetic analogues retain the ability to bind to their cellular receptor, peptidoglycan intermediate lipid II. American Chemical Society 2019-10-28 2019-11-27 /pmc/articles/PMC6887851/ /pubmed/31657913 http://dx.doi.org/10.1021/acs.jmedchem.9b01078 Text en Copyright © 2019 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
spellingShingle Bann, Samantha J.
Ballantine, Ross D.
McCallion, Conor E.
Qian, Pei-Yuan
Li, Yong-Xin
Cochrane, Stephen A.
A Chemical-Intervention Strategy To Circumvent Peptide Hydrolysis by d-Stereoselective Peptidases
title A Chemical-Intervention Strategy To Circumvent Peptide Hydrolysis by d-Stereoselective Peptidases
title_full A Chemical-Intervention Strategy To Circumvent Peptide Hydrolysis by d-Stereoselective Peptidases
title_fullStr A Chemical-Intervention Strategy To Circumvent Peptide Hydrolysis by d-Stereoselective Peptidases
title_full_unstemmed A Chemical-Intervention Strategy To Circumvent Peptide Hydrolysis by d-Stereoselective Peptidases
title_short A Chemical-Intervention Strategy To Circumvent Peptide Hydrolysis by d-Stereoselective Peptidases
title_sort chemical-intervention strategy to circumvent peptide hydrolysis by d-stereoselective peptidases
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887851/
https://www.ncbi.nlm.nih.gov/pubmed/31657913
http://dx.doi.org/10.1021/acs.jmedchem.9b01078
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