Studies of polyethylene glycol modification of HM-3 polypeptides

摘要

An RGD modified endostatin-derived synthetic peptide, named HM-3, is a polypeptide angiogenesis inhibitor previously synthesized in our laboratory. Its robust inhibitory effects on endothelial cell migration and tumor growth have been demonstrated by in vivo and in vitro activity assays. However, the drug has relatively short half life in vivo. The current study designed to prolong HM-3 half life, we used methoxy-polyethylene glycol-aldehyde (mPEG-ALD) to specifically modify its N terminus, and the maximal modification rate was achieved. Compared with HM-3, the newly modified PEG10k-HM-3 was shown to be more active in the inhibition of angiogenesis in the chorioallantoic membrane of chick embryos (CAM), its rate of in vitro degradation in serum was markedly reduced, and its in vivo half life was prolonged by 5. 86 fold relative to unmodified HM-3 after intravenous injection into male SD rats.