Direct modifications of the cyclic peptide Polymyxin B leading to analogues with enhanced in vitro antibacterial activity

https://doi.org/10.1016/j.bmcl.2020.127163Get rights and content

Abstract

Synthetic modifications have been made directly to the cyclic peptide core of polymyxin B, enabling the further understanding of structure activity relationships of this antimicrobial peptide. Such modified polymyxins are also substrates for enzymic hydrolysis, enabling the synthesis of a variety of semi-synthetic analogues, resulting in compounds with increased in vitro antibacterial activity.

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Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

This work was partially supported by a grant awarded to Cantab Anti-infectives Ltd by Innovate UK under the Biomedical Catalyst scheme. This work has been funded in part with US Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract HHSN272201500014C. Strains with reduced susceptibility to Polymyxin B were obtained from IHMA Europe Sàrl, Monthey, Switzerland. Cytotoxicity assays were

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