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From Discovery of Snake Venom Disintegrins to A Safer Therapeutic Antithrombotic Agent

1
Department of Medicine, Mackay Medical College, New Taipei City 25245, Taiwan
2
Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan
*
Author to whom correspondence should be addressed.
Toxins 2019, 11(7), 372; https://doi.org/10.3390/toxins11070372
Received: 2 June 2019 / Revised: 22 June 2019 / Accepted: 24 June 2019 / Published: 26 June 2019
(This article belongs to the Special Issue From Toxins to Drugs)
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Abstract

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. View Full-Text
Keywords: snake venom proteins; disintegrins; antiplatelet agent; arterial thrombosis; angiogenesis; septic inflammation snake venom proteins; disintegrins; antiplatelet agent; arterial thrombosis; angiogenesis; septic inflammation
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Kuo, Y.-J.; Chung, C.-H.; Huang, T.-F. From Discovery of Snake Venom Disintegrins to A Safer Therapeutic Antithrombotic Agent. Toxins 2019, 11, 372.

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