Synthesis and preliminary anti-diabetic activity evaluation of novel PEGylated GLP-1 receptor agonists

In order to obtain glucagon-like peptide-1(GLP-1)analogs which can sustainedly control the levels of glucose, 12 derivatives were designed and synthesized by coupling monomethoxy polyethylene glycol(mPEG, with average molecular weights of 350, 550 and 750)to GLP-1 analogs. Preliminary pharmacological activities showed that all compounds retained GLP-1 receptor agonist activities, and the hypoglycemic activity of compound I - 12 was similar to those of Ex-4 and Liraglutide, suggesting I - 12 could be a potential long-acting GLP-1 receptor agonist.