Peptide-oligourea Hybrids Analogue of GLP-1 with Improved Action in Vivo

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Feb 27

PMID 30804332

Citations 22

Authors

Juliette Fremaux

Claire Venin

Laura Mauran

Robert H Zimmer

Gilles Guichard

Sebastien R Goudreau

Affiliations

Soon will be listed here.

Abstract

Peptides have gained so much attention in the last decade that they are now part of the main strategies, with small molecules and biologics, for developing new medicines. Despite substantial progress, the successful development of peptides as drugs still requires a number of limitations to be addressed, including short in vivo half-lives and poor membrane permeability. Here, we describe the use of oligourea foldamers as tool to improve the pharmaceutical properties of GLP-1, a 31 amino acid peptide hormone involved in metabolism and glycemic control. Our strategy consists in replacing four consecutive amino acids of GLP-1 by three consecutive ureido residues by capitalizing on the structural resemblance of oligourea and α-peptide helices. The efficacy of the approach is demonstrated with three GLP-1-oligourea hybrids showing prolonged activity in vivo. Our findings should enable the use of oligoureas in other peptides to improve their pharmaceutical properties and may provide new therapeutic applications.

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