Hydrocarbon-Stitched Peptide Agonists of Glucagon-Like Peptide-1 Receptor.

ABSTRACT: Glucagon-like peptide 1 (GLP-1) is a natural peptide agonist of the GLP-1 receptor (GLP-1R) found on pancreatic β-cells. Engagement of the receptor stimulates insulin release in a glucose-dependent fashion and increases β-cell mass, two ideal features for pharmacologic management of type 2 diabetes. Thus, intensive efforts have focused on developing GLP-1-based peptide agonists of GLP-1R for therapeutic application. A primary challenge has been the naturally short half-life of GLP-1 due to its rapid proteolytic degradation in vivo. Whereas mutagenesis and lipidation strategies have yielded clinical agents, we developed an alternative approach to preserving the structure and function of GLP-1 by all-hydrocarbon i, i + 7 stitching. This particular "stitch" is especially

SUBMITTER: Bird GH 

PROVIDER: S-EPMC7366314 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature