From Discovery of Snake Venom Disintegrins to A Safer Therapeutic Antithrombotic Agent
Snake venoms affect blood coagulation and platelet function in diverse ways. Some venom components inhibit platelet function, while other components induce platelet aggregation. Among the platelet aggregation inhibitors, disintegrins have been recognized as unique and potentially valuable tools for...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-06-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/11/7/372 |
| _version_ | 1797999373562413056 |
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| author | Yu-Ju Kuo Ching-Hu Chung Tur-Fu Huang |
| author_facet | Yu-Ju Kuo Ching-Hu Chung Tur-Fu Huang |
| author_sort | Yu-Ju Kuo |
| collection | DOAJ |
| description | Snake venoms affect blood coagulation and platelet function in diverse ways. Some venom components inhibit platelet function, while other components induce platelet aggregation. Among the platelet aggregation inhibitors, disintegrins have been recognized as unique and potentially valuable tools for examining cell−matrix and cell−cell interactions and for the development of antithrombotic and antiangiogenic agents according to their anti-adhesive and anti-migration effect on tumor cells and antiangiogenesis activities. Disintegrins represent a family of low molecular weight, cysteine-rich, Arg-Gly-Asp(RGD)/Lys-Gly-Asp(KGD)-containing polypeptides, which inhibit fibrinogen binding to integrin αIIbβ3 (i.e., platelet glycoprotein IIb/IIIa), as well as ligand binding to integrins αvβ3, and α5β1 expressed on cells (i.e., fibroblasts, tumor cells, and endothelial cells). This review focuses on the current efforts attained from studies using disintegrins as a tool in the field of arterial thrombosis, angiogenesis, inflammation, and tumor metastasis, and briefly describes their potential therapeutic applications and side effects in integrin-related diseases. Additionally, novel R(K)GD-containing disintegrin TMV-7 mutants are being designed as safer antithrombotics without causing thrombocytopenia and bleeding. |
| first_indexed | 2024-04-11T11:03:43Z |
| format | Article |
| id | doaj.art-100c7132db404e02abc2f16149407667 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-11T11:03:43Z |
| publishDate | 2019-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-100c7132db404e02abc2f161494076672022-12-22T04:28:26ZengMDPI AGToxins2072-66512019-06-0111737210.3390/toxins11070372toxins11070372From Discovery of Snake Venom Disintegrins to A Safer Therapeutic Antithrombotic AgentYu-Ju Kuo0Ching-Hu Chung1Tur-Fu Huang2Department of Medicine, Mackay Medical College, New Taipei City 25245, TaiwanDepartment of Medicine, Mackay Medical College, New Taipei City 25245, TaiwanDepartment of Medicine, Mackay Medical College, New Taipei City 25245, TaiwanSnake venoms affect blood coagulation and platelet function in diverse ways. Some venom components inhibit platelet function, while other components induce platelet aggregation. Among the platelet aggregation inhibitors, disintegrins have been recognized as unique and potentially valuable tools for examining cell−matrix and cell−cell interactions and for the development of antithrombotic and antiangiogenic agents according to their anti-adhesive and anti-migration effect on tumor cells and antiangiogenesis activities. Disintegrins represent a family of low molecular weight, cysteine-rich, Arg-Gly-Asp(RGD)/Lys-Gly-Asp(KGD)-containing polypeptides, which inhibit fibrinogen binding to integrin αIIbβ3 (i.e., platelet glycoprotein IIb/IIIa), as well as ligand binding to integrins αvβ3, and α5β1 expressed on cells (i.e., fibroblasts, tumor cells, and endothelial cells). This review focuses on the current efforts attained from studies using disintegrins as a tool in the field of arterial thrombosis, angiogenesis, inflammation, and tumor metastasis, and briefly describes their potential therapeutic applications and side effects in integrin-related diseases. Additionally, novel R(K)GD-containing disintegrin TMV-7 mutants are being designed as safer antithrombotics without causing thrombocytopenia and bleeding.https://www.mdpi.com/2072-6651/11/7/372snake venom proteinsdisintegrinsantiplatelet agentarterial thrombosisangiogenesisseptic inflammation |
| spellingShingle | Yu-Ju Kuo Ching-Hu Chung Tur-Fu Huang From Discovery of Snake Venom Disintegrins to A Safer Therapeutic Antithrombotic Agent Toxins snake venom proteins disintegrins antiplatelet agent arterial thrombosis angiogenesis septic inflammation |
| title | From Discovery of Snake Venom Disintegrins to A Safer Therapeutic Antithrombotic Agent |
| title_full | From Discovery of Snake Venom Disintegrins to A Safer Therapeutic Antithrombotic Agent |
| title_fullStr | From Discovery of Snake Venom Disintegrins to A Safer Therapeutic Antithrombotic Agent |
| title_full_unstemmed | From Discovery of Snake Venom Disintegrins to A Safer Therapeutic Antithrombotic Agent |
| title_short | From Discovery of Snake Venom Disintegrins to A Safer Therapeutic Antithrombotic Agent |
| title_sort | from discovery of snake venom disintegrins to a safer therapeutic antithrombotic agent |
| topic | snake venom proteins disintegrins antiplatelet agent arterial thrombosis angiogenesis septic inflammation |
| url | https://www.mdpi.com/2072-6651/11/7/372 |
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