Cargando…

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...

Descripción completa

Detalles Bibliográficos
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
Descripción
Sumario:[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.