Indexed on: 27 Aug '08Published on: 27 Aug '08Published in: International Journal of Peptide Research and Therapeutics
Two different chemical classes of putative amide-based prodrugs of glucagon-like peptide-1 (GLP), one with an amino and the other with α hydroxyl terminal extension have been synthesized and biochemically characterized. The conversion of these terminally-extended peptide hormone analogs to a peptide of much enhanced potency through cyclization of the terminal dipeptide was studied under physiological conditions. The peptides studied demonstrated great stability and little propensity to cyclize to DKP and DMP under physiological conditions. These results stand in contrast to previous reports with model amide-based peptides and indicate that such cleavage is unlikely in larger peptides constituted by naturally coded amino acids.