Releasable and traceless PEGylation of arginine-rich antimicrobial peptides

Chemical Science
Yuhui GongMarc A Gauthier

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.

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Citations

Aug 24, 2017·Chemistry : a European Journal·Ashok Khanal, Shiyue Fang
Sep 5, 2019·Pharmaceutics·Ángela Martin-SerranoF Javier de la Mata
May 22, 2018·Chemical Science·Alicia C McGeachyFranz M Geiger
Dec 19, 2020·International Journal of Molecular Sciences·Stanislav R KurpeOxana V Galzitskaya
Jun 22, 2021·Future Medicinal Chemistry·Zi-Zhen ZengYang Wan
Jul 24, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Shahin AghamiriMojgan Bandehpour
Jul 7, 2021·Chembiochem : a European Journal of Chemical Biology·Christine M ArtimChristopher A Alabi
Aug 5, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Yang ZhouJun Wu
Jun 28, 2017·Biochemistry·Justine N deGruyterPhil S Baran
Oct 16, 2021·Chemical Communications : Chem Comm·Samilla B RezendeMarlon H Cardoso

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