Releasable and traceless PEGylation of arginine-rich antimicrobial peptides

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. <i>In vitro</i>, conjugates were insensitive to serum proteases, and released native AMP with full <i>in vitro</i> 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.