In vitro and in vivo antiangiogenic activity of a novel deca-peptide derived from human tissue-type plasminogen activator kringle 2.
A synthetic deca-peptide corresponding to the amino acid sequence Arg(54)-Trp(63) of human tissue-type plasminogen activator (t-PA) kringle 2 domain, named TKII-10, is produced and tested for its ability to inhibit endothelial cell proliferation, migration, tube formation in vitro, and angiogenesis in vivo. At the same time, another peptide TKII-10S composed of the same 10 amino acids as TKII-10, but in a different sequence, is also produced and tested. The results show that TKII-10 potently inhibits VEGF-stimulated endothelial cell migration and tube formation in a dose-dependent, as well as sequence-dependent, manner in vitro while it is inactive in inhibiting endothelial cell proliferation. Furthermore, TKII-10 potently inhibits angiogenesis in chick chorioallantoic membrane and mouse cornea. The middle four amino acids DGDA in their sequence play an important role in TKII-10 angiogenesis inhibition(.) These results suggest that TKII-10 is a novel angiogenesis inhibitor that may serve as a prototype for antiangiogenic drug development.
Su
Li
L
Department of Ophthalmology, Shanghai First People's Hospital, Affiliate of Shanghai Jiaotong University, No. 100 Haining Road, Shanghai 200080, PR China.
Xu
Xun
X
Zhao
Hui
H
Gu
Qing
Q
Zou
Haidong
H
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D003315:Cornea / Q000098:blood supply / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D018082:Kringles; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010959:Tissue Plasminogen Activator / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D009842:Oligopeptides; D010446:Peptide Fragments; D042461:Vascular Endothelial Growth Factor A; C550736:arginyl-asparagyl-prolyl-aspartyl-glycyl-aspartyl-alanyl-lysyl-prolyl-tryptophan; D010959:Tissue Plasminogen Activator