A peptide derived from human prothrombin fragment 2 inhibits prothrombinase and angiogenesis.
We constructed the synthetic peptide library representing human prothrombin fragment 2 (F2) sequence and explored the inhibitory sequence for prothrombinase, which was reconstituted in vitro by adding factor Xa, factor Va, and calcium into phospholipids. The nonapeptide NSAVLQVEN (NSA9) suppressed prothrombinase reconstituted not only on phospholipid vesicles but also on the bovine capillary endothelial (BCE) cell surface. Kinetic analyses demonstrated that NSA9 is a mixed-type inhibitor of Xa. Furthermore, the nonapeptide inhibited the proliferation of BCE cells and also suppressed angiogenesis in chicken embryos. The inhibitory activities of NSA9 were abrogated by pre-incubation with anti-F2 monoclonal antibody, 4E7. These data demonstrate that anti-angiogenic activity of F2 may be related to its ability to inhibit prothrombinase.
Kim
Bum Joon
BJ
Department of Biochemistry, College of Science, Yonsei University, 120-749, Seoul, South Korea.
Koo
So Young
SY
Kim
Soung Soo
SS
D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002196:Capillaries / Q000166:cytology / Q000187:drug effects; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002642:Chick Embryo; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology* / Q000502:physiology*; D019151:Peptide Library; D011516:Prothrombin / Q000737:chemistry / Q000502:physiology*; D013925:Thromboplastin / Q000037:antagonists & inhibitors*
D020533:Angiogenesis Inhibitors; D010446:Peptide Fragments; D019151:Peptide Library; C044183:prothrombin fragment 2; D011516:Prothrombin; D013925:Thromboplastin