Effect of RGD-4C position is more important than disulfide bonds on antiangiogenic activity of RGD-4C modified endostatin derived synthetic polypeptide.
ES-2 (IVRRADRAAVP), an endostatin-derived synthetic polypeptide, contains the amino acids 50-60 of endostatin from its N terminus, and it had no inhibitory effects on tumor growth in vivo. In order to increase the targeted delivery of ES-2 to tumors and further enhance the activity, the polypeptide RGD-4C (ACDCRGDCFC) was introduced into ES-2, and the effects of RGD-4C position and RGD-4C disulfide bonds on polypeptides activity were investigated. When RGD-4C polypeptides (with or without disulfide bonds) were introduced to the N-terminals of synthesized ES-2, the modified ES-2 showed significant antitumor activity in vivo. Cell proliferation and chicken chorioallantoic membrane (CAM) assay results showed that disulfide bonds had no significant effects on RGD-4C-modified ES-2 antiangiogenic activity. Furthermore, the target of modified peptides was integrin alpha5beta1, rather than integrin alphavbeta3 as previous studies mentioned.
Department of Marine Pharmacy, College of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, P. R. China.
Runting
R
Yin
Heng
H
Zheng
Tao
T
Xi
Han-Mei
HM
Xu
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001667:Binding, Competitive; D002417:Cattle; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000187:drug effects; D004220:Disulfides / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D043169:Endostatins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects*; D005260:Female; D006801:Humans; D039081:Integrin alpha5beta1 / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
C000607498:AP25 peptide; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D004220:Disulfides; D043169:Endostatins; D039081:Integrin alpha5beta1; D010446:Peptide Fragments; D010455:Peptides