Antiplasmin activity of a peptide that binds to the receptor-binding site of angiogenin.
It has been suggested that angiogenin binds to an actin-like molecule present on the surface of endothelial cells. Actin inhibits plasmin activity, but the angiogenin-actin complex is not active. In this report, we found that plasmin inhibits the interaction between angiogenin and actin suggesting a possibility that both angiogenin and plasmin may bind to a similar site on actin. Here we report that chANG, an antiangiogenin peptide that binds to the actin-binding site of angiogenin, inhibits the proteolytic activity of plasmin without any apparent effect on the activities of plasminogen activators and matrix metalloproteases. Its antiplasmin activity is comparable with that of actin. chANG inhibits plasmin activity via its binding to plasmin kringle domains while scrambled chANG does not bind to plasmin. chANG also inhibits the invasion of angiogenin-secreting human fibrosarcoma and colorectal carcinoma cells without effecting migration. Furthermore, chANG blocks angiogenesis induced by fibrosarcoma cells and metastasis of colorectal carcinoma cells to the liver. Therefore, the 11-amino acid peptide chANG has both antiangiogenin and antiplasmin activity, and could be useful in the development of anticancer agents.
Gho
Yong Song
YS
Department of Life Science, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Korea.
Yoon
Wan-Hee
WH
Chae
Chi-Bom
CB
D016475:3T3 Cells; D000199:Actins / Q000737:chemistry; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D001665:Binding Sites; D019921:Biotinylation; D002465:Cell Movement; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005341:Fibrinolysin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D051379:Mice; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012259:Ribonuclease, Pancreatic / Q000737:chemistry* / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured; D000979:alpha-2-Antiplasmin / Q000378:metabolism*
D000199:Actins; D016588:Anticarcinogenic Agents; D010455:Peptides; D000979:alpha-2-Antiplasmin; C046366:angiogenin; D012259:Ribonuclease, Pancreatic; D005341:Fibrinolysin