From discovery of snake venom disintegrins to a safer therapeutic antithrombotic agent
Journal
Toxins
Journal Volume
11
Journal Issue
7
Pages
372
Date Issued
2019
Author(s)
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. ? 2019 by the authors. Licensee MDPI, Basel, Switzerland.
Subjects
Angiogenesis; Antiplatelet agent; Arterial thrombosis; Disintegrins; Septic inflammation; Snake venom proteins
SDGs
Other Subjects
abciximab; anticoagulant agent; disintegrin; eptifibatide; fibrinogen; fibrinogen receptor; reactive oxygen metabolite; rhodostomin; tirofiban; tissue plasminogen activator; toll like receptor 2; trifavin; trigramin; unclassified drug; vitronectin; antiinflammatory agent; antineoplastic agent; antithrombocytic agent; disintegrin; fibrinolytic agent; integrin; snake venom; angiogenesis; antiangiogenic activity; antiinflammatory activity; antineoplastic activity; artery thrombosis; atherosclerosis; binding site; bleeding; blood clotting; brain ischemia; cell adhesion; cell interaction; cell migration; drug safety; gene mutation; Glanzmann disease; heart infarction; hemostasis; immune response; inflammation; ligand binding; metastasis; molecular docking; restenosis; Review; thrombocyte aggregation; thrombocyte function; thrombocytopenia; thrombosis; transluminal coronary angioplasty; X ray crystallography; animal; chemistry; human; Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Disintegrins; Fibrinolytic Agents; Humans; Integrins; Platelet Aggregation Inhibitors; Snake Venoms
Type
review