Department of Chemistry, Biochemistry Laboratory, Federal University of Lavras (UFLA), Lavras, Minas Gerais, 37200-000, Brazil.
Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of Sao Paulo (FCFRP-USP), Ribeirão Preto-SP, Brazil.
Curr Drug Targets. 2019;20(4):465-477. doi: 10.2174/1389450119666181022154737.
Disintegrins are non-enzymatic proteins that interfere on cell-cell interactions and signal transduction, contributing to the toxicity of snake venoms and play an essential role in envenomations. Most of their pharmacological and toxic effects are the result of the interaction of these molecules with cell surface ligands, which has been widely described and studied. These proteins may act on platelets, leading to hemorrhage, and may also induce apoptosis and cytotoxicity, which highlights a high pharmacological potential for the development of thrombolytic and antitumor agents. Additionally, these molecules interfere with the functions of integrins by altering various cellular processes such as migration, adhesion and proliferation. This review gathers information on functional characteristics of disintegrins isolated from snake venoms, emphasizing a comprehensive view of the possibility of direct use of these molecules in the development of new drugs, or even indirectly as structural models.
disintegrins 是一种非酶类蛋白质,能干扰细胞间相互作用和信号转导,促进蛇毒的毒性,并在蛇咬伤中发挥重要作用。它们的大多数药理学和毒性作用是这些分子与细胞表面配体相互作用的结果,这已经被广泛描述和研究。这些蛋白质可能作用于血小板,导致出血,也可能诱导细胞凋亡和细胞毒性,这突出了开发溶栓和抗肿瘤药物的高药理学潜力。此外,这些分子通过改变迁移、黏附和增殖等各种细胞过程来干扰整合素的功能。本综述收集了从蛇毒中分离出的 disintegrins 的功能特征信息,强调了直接将这些分子用于新药开发的可能性,甚至作为结构模型的间接可能性。