%0 PDF %T Molecular Design of Therapeutics for the Treatment of Type II Diabetes and Cardiovascular Disease. %A Du, Jasper L. %D 2017-05-20 19:39:20 -0400 %8 2017-05-20 %I Tufts Archival Research Center %R http://localhost/files/5d86pb46s %X Glucose-dependent insulinotropic peptide (GIP) is a 31-amino acid peptide hormone that is secreted by K-cells to regulate postprandial glucose levels. By binding to its receptor, GIPR, GIP mediates several beneficial effects such as improved insulin sensitivity, increased β-cell mass, and increased energy consumption. However, dipeptidyl peptidase-4 (DPP-4) rapidly inactivates GIP, within 5-7 min. Efforts to extend DPP-4 targeted peptides have included inhibition of DPP-4 and lipidation of peptides. Here, synthesis of a N-trifluoroethyl and lipidated GIP was completed. The N-trifluoroethyl alkylation of GIP confers proteolytically resistant properties in vitro, providing complete resistance to overnight incubations with DPP-4. Compared to native GIP in vivo, the N-terminally protected and lipidated GIP remained in circulation at 800x and 80x higher concentrations, owing to the DPP-4 resistance and lipidiation. %G eng %[ 2022-10-07 %~ Tufts Digital Library %W Institution