Mardirossian, M; Sola, R; Beckert, B; Collis, DWP; Di Stasi, A; Armas, F; Hilpert, K; Wilson, DN; Scocchi, M
(2019)
Proline-Rich Peptides with Improved Antimicrobial Activity against E. coli, K. Pneumoniae, and A. Baumannii.
ChemMedChem, 14 (24).
pp. 2025-2033.
ISSN 1860-7187
https://doi.org/10.1002/cmdc.201900465
SGUL Authors: Hilpert, Kai
Abstract
Proline-rich antimicrobial peptides (PrAMPs) are promising agents to combat multi-drug resistant pathogens due to a high antimicrobial activity, yet low cytotoxicity. A library of derivatives of the PrAMP Bac5(1-17) was synthesized and screened to identify which residues are relevant for its activity. In this way, we discovered that two central motifs -PIRXP- cannot be modified, while residues at N- and C- termini tolerated some variations. We found five Bac5(1-17) derivatives bearing 1-5 substitutions, with an increased number of arginine and/or tryptophan residues, exhibiting improved antimicrobial activity and broader spectrum of activity while retaining low cytotoxicity toward eukaryotic cells. Transcription/translation and bacterial membrane permeabilization assays showed that these new derivatives still retained the ability to strongly inhibit bacterial protein synthesis, but also acquired permeabilizing activity to different degrees. These new Bac5(1-17) derivatives therefore show a dual mode of action which could hinder the selection of bacterial resistance against these molecules.
Item Type: |
Article
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Additional Information: |
© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: |
Antibiotics, membrane permeabilization, proline-rich peptide, protein synthesis inhibition, solid-phase synthesis, Antibiotics, membrane permeabilization, proline-rich peptide, protein synthesis inhibition, solid-phase synthesis, antibiotics, membrane permeabilization, proline-rich peptide, protein synthesis inhibition, solid-phase synthesis, 0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, 1115 Pharmacology and Pharmaceutical Sciences, Medicinal & Biomolecular Chemistry |
SGUL Research Institute / Research Centre: |
Academic Structure > Infection and Immunity Research Institute (INII) |
Journal or Publication Title: |
ChemMedChem |
ISSN: |
1860-7187 |
Language: |
eng |
Dates: |
Date | Event |
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17 December 2019 | Published | 14 November 2019 | Published Online | 31 October 2019 | Accepted |
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Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
Project ID | Funder | Funder ID |
---|
UNSPECIFIED | University of Trieste | UNSPECIFIED | UNSPECIFIED | "Made in Trieste" by Area Science Park (Trieste) | UNSPECIFIED | UNSPECIFIED | Institute of Infection and Immunity | UNSPECIFIED | DLR01Kl1820 | Deutsche Zentrum für Luft- und Raumfahrt | UNSPECIFIED |
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PubMed ID: |
31692278 |
Web of Science ID: |
WOS:000496281800001 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/111369 |
Publisher's version: |
https://doi.org/10.1002/cmdc.201900465 |
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