Albumin binding of insulins acylated with fatty acids: characterization of the ligand-protein interaction and correlation between binding affinity and timing of the insulin effect in vivo

摘要: Albumin is a multifunctional transport protein that binds wide variety of endogenous substances and drugs. Insulins with affinity for albumin were engineered by acylation the epsilon-amino group LysB29 saturated fatty acids containing 10-16 carbon atoms. The association constants binding acid acylated insulins to human are in order 10(4)-10(5) M-1. apparently involves both non-polar ionic interactions protein. bind at long-chain sites, but lower than free depends relatively small degree on number atoms chain. Differences reflected relative timing blood-glucose-lowering effect after subcutaneous injection into rabbits. provide breakthrough search soluble, prolonged-action insulin preparations basal delivery hormone diabetic patient. We conclude biochemical concept can be applied protract insulin, suggest derivatization albumin-binding ligands could generally applicable prolong action profile peptide