Ved Srivastava

Discovery of Novel and Long Acting GLP-1 Analogs

Glucagon Like Peptide-1 (GLP-1) is a 30 amino acid gut hormone produced by intestinal L cells and pancreatic α cells. GLP-1 induces post prandial glucose-dependent insulin secretion and inhibits gastric secretion and motility, thus reducing circulating glucose levels and increasing satiety. These physiological effects make GLP-1 an interesting target for both diabetes and obesity therapy. However, GLP-1 lacks the therapeutic potential due to its very short half-life. Described are our efforts using ortholog screening and fragment substitution to discover novel and long acting GLP-1 analogues with modifications in the GLP-1 sequence, HGEGTFTSDLTEYLEEEAVREFIEWLKNGGPKKIRYS-NH2. These analogs have desired potency and efficacy over endogenous GLP-1 with a 15h duration of action in an acute food intake reduction mouse model.