Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

A Desmethylphosphinothricin Dipeptide Derivative Effectively Inhibits Escherichia coli and Bacillus subtilis Growth

Version 1 : Received: 29 August 2023 / Approved: 30 August 2023 / Online: 31 August 2023 (13:18:01 CEST)

A peer-reviewed article of this Preprint also exists.

Khomutov, M.A.; Giovannercole, F.; Onillon, L.; Demiankova, M.V.; Vasilieva, B.F.; Salikhov, A.I.; Kochetkov, S.N.; Efremenkova, O.V.; Khomutov, A.R.; De Biase, D. A Desmethylphosphinothricin Dipeptide Derivative Effectively Inhibits Escherichia coli and Bacillus subtilis Growth. Biomolecules 2023, 13, 1451. Khomutov, M.A.; Giovannercole, F.; Onillon, L.; Demiankova, M.V.; Vasilieva, B.F.; Salikhov, A.I.; Kochetkov, S.N.; Efremenkova, O.V.; Khomutov, A.R.; De Biase, D. A Desmethylphosphinothricin Dipeptide Derivative Effectively Inhibits Escherichia coli and Bacillus subtilis Growth. Biomolecules 2023, 13, 1451.

Abstract

New antibiotics are unquestionably needed in the fight to the emergence and spread of multidrug-resistant bacteria. So far, antibiotics targeting bacterial central metabolism have been poorly investigated. By determining the minimal inhibitory concentration (MIC) of desmethylphosphinothricin (Glu-γ-PH), an analogue of glutamate with a phosphinic moiety re-placing the γ-carboxyl group, we previously showed its promising antibacterial activity on Escherichia coli. Herein we synthetized and determined the growth inhibition exerted on E. coli by an L-Leu dipeptide derivative of Glu-γ-PH (L-Leu-D,L-Glu-γ-PH). Furthermore, we compared the growth inhibition obtained with this dipeptide with that exerted by the free amino acid, i.e. Glu-γ-PH, and by their phosphonic and non-desmethylated analogues. All tested compounds were more effective when assayed in chemically defined minimal medium. The dipeptide L-Leu-D,L-Glu-γ-PH had a significantly improved antibacterial activity (2 μg/mL), at a concentra-tion between the non-desmethytaled (0.1 μg/mL) and the phosphonic (80 μg/mL) analogues. Also in Bacillus subtilis the dipeptide L-Leu-D,L-Glu-γ-PH displayed an activity comparable to that of the antibiotic amoxicillin. This work highlights the antibacterial relevance of the phosphinic pharmacophore and proposes new avenues to the development of novel antimicrobial drugs containing the phosphinic moiety.

Keywords

antibacterial; glutamate metabolism; antimicrobial resistance; central metabolism; dipeptide permeases; phosphorus-containing glutamate analogues

Subject

Biology and Life Sciences, Other

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.