An Integrated Strategy for Improving Plasma Half-life of Therapeutic Peptides

摘要

Peptides are viable biopharmaceutical agents because of their superior specificity and their smaller size [1]. The clinical application of peptides has been limited by their susceptibility to proteolysis. Of many strategies for improving their pharmacokinetics, coupling therapeutic peptides to serum albumin or a peptide (protein) domain that will allow association with albumin, represents a promising strategy for extending the circulation half-life (t_(1/2)) of peptides [2-3]. In this work, we demonstrate the application of native plasma proteases to sustained release albumin-protected peptides in order to achieve the effective peptide concentration in vivo, using glucagon like peptide-1 (GLP-1), a potent therapeutic peptide for Type 2 diabetes [4], as model.