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

ABSTRACT: 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. In vitro assays confirmed that synthetic analogues retain the ability to bind to their cellular receptor, peptidoglycan intermediate lipid II.

SUBMITTER: Bann SJ

PROVIDER: S-EPMC6887851 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Bann Samantha J SJ Ballantine Ross D RD McCallion Conor E CE Qian Pei-Yuan PY Li Yong-Xin YX Cochrane Stephen A SA

Journal of medicinal chemistry 20191108 22

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. <i>In</i> <i>vitro</i> assays confirmed that synthetic analogues retain t ...[more]

PMID: 31657913

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