Application of self assembling peptide as drug carrier for extending the GLP-1 stability

The multiple physiological characterizations of glucagon-like peptide-1 (GLP-1) make it a promising drug candidate for the therapy of type 2 diabetes. However, the extremely poor stability of GLP-1, proteolysis by dipeptidyl peptidase-IV (DPP IV), limits its development in the clinical utility significantly. In order to avoid the pocket docking of GLP-1 against DPP IV, self assembling peptide was employed in this study. Self assembling peptide (pp1) is capable of forming supramolecule contain a cavity which load GLP-1 molecules inside. In this study, the formation procedure of GLP-1/pp1 complex was computationally simulated, in order to further investigate the interaction between GLP-1 and pp1. In this study, the amino acid residues in GLP-1 and pp1 those involved in forming hydrogen bonds were ascertained which benefits the further mutation and improvement on pp1. In addition, the glucose tolerance test in rodent animals was employed to ascertain the prolonged stability of GLP-1 followed the complex formation with pp1. Our results clarified the mechanism of the formation of GLP-1 and pp1 stable complex, which is significant for its development into clinical trial.