Novel mono-lipidated dimeric glucagon-like peptide-1 receptor agonist with improved long-acting and hypoglycemic activity.

ABSTRACT: Dimerization is a useful tool to boost ligand-receptor interaction. Both lipidation and dimerization effectively prolong the short half-life (t _1/2) of peptides by facilitating binding with serum albumin and increasing hydrodynamic size. Here, we described two novel GLP-1 conjugates with high glucagon-like peptide-1 (GLP-1) receptor activation potencies, dimerized GLP-1 (Di-GLP-1) and lipidated Di-GLP-1 (Lip-Di-GLP-1). Di-GLP-1 and Lip-Di-GLP-1 were prepared through cysteine-maleimide specific coupling reactions using Gly₈-Cys₃₁-GLP-1, bis-maleimide amine, and activated palmitic acid. The receptor activation potencies of Di-GLP-1 and Lip-Di-GLP-1 were 13.6-fold and 9.5-fold higher than GLP-1, respectively. The in vivo hypoglycemic and insulino

SUBMITTER: Sun L 

PROVIDER: S-EPMC9062351 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature