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Releasable and traceless PEGylation of arginine-rich antimicrobial peptides

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Abstract

Arginine-rich antimicrobial peptides (AMPs) are emerging therapeutics of interest. However, their applicability is limited by their short circulation half-life, caused in part by their small size and digestion by blood proteases. This study reports a strategy to temporarily mask arginine residues within AMPs with methoxy poly(ethylene glycol). Based on the reagent used, release of AMPs occurred in hours to days in a completely traceless fashion. In vitro, conjugates were insensitive to serum proteases, and released native AMP with full in vitro bioactivity. This strategy is thus highly relevant and should be adaptable to the entire family of arginine-rich AMPs. It may potentially be used to improve AMP-therapies by providing a more steady concentration of AMP in the blood after a single injection, avoiding toxic effects at high AMP doses, and reducing the number of doses required over the treatment duration.

Graphical abstract: Releasable and traceless PEGylation of arginine-rich antimicrobial peptides

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Publication details

The article was received on 17 Feb 2017, accepted on 21 Mar 2017 and first published on 30 Mar 2017


Article type: Edge Article
DOI: 10.1039/C7SC00770A
Citation: Chem. Sci., 2017, Advance Article
  • Open access: Creative Commons BY license
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    Releasable and traceless PEGylation of arginine-rich antimicrobial peptides

    Y. Gong, D. Andina, S. Nahar, J.-C. Leroux and M. A. Gauthier, Chem. Sci., 2017, Advance Article , DOI: 10.1039/C7SC00770A

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