Albumin-binding domain extends half-life of glucagon-like peptide-1

Glucagon-like peptide-1 (GLP-1) is considered to be a promising peptide for the treatment of type 2 diabetes mellitus (T2DM). However, extremely short half-life GLP-1 limits its clinical application. Albumin-binding domain (ABD) with high affinity human serum albumin (HSA) has been used widely extension therapeutic peptides and proteins. In present study, novel receptor agonists were designed by genetic fusion three kinds ABDs different affinities HSA: GA3, ABD035 ABDCon. The bioactivities half-lives ABD-fusion proteins types lengths linkers investigated in vitro vivo. results demonstrated that could bind HSA affinity. blood glucose-lowering effect was significantly improved sustained ABD. Meanwhile, inhibited food intake, which beneficial T2DM obesity treatment. substantially extended virtue vivo also showed longer linker inserted between ABD resulted higher effect. generated ABDCon exhibited similar pharmacokinetics These findings demonstrate retain natural can further developed weight loss. It indicates strategy generally applicable any or protein, improve pharmacodynamic pharmacokinetic properties.