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.
Yin
Runting
R
Department of Marine Pharmacy, College of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, P. R. China.
Zheng
Heng
H
Xi
Tao
T
Xu
Han-Mei
HM
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