Almeida Gabriela de Oliveira, de Oliveira Isadora Sousa, Arantes Eliane Candiani, Sampaio Suely Vilela
Department of Clinical Analysis, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Department of BioMolecular Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
J Venom Anim Toxins Incl Trop Dis. 2023 Sep 18;29:e20230039. doi: 10.1590/1678-9199-JVATITD-2023-0039. eCollection 2023.
Snake venom disintegrins are low molecular weight, non-enzymatic proteins rich in cysteine, present in the venom of snakes from the families Viperidae, Crotalidae, Atractaspididae, Elapidae, and Colubridae. This family of proteins originated in venom through the proteolytic processing of metalloproteinases (SVMPs), which, in turn, evolved from a gene encoding an A Disintegrin And Metalloprotease (ADAM) molecule. Disintegrins have a recognition motif for integrins in their structure, allowing interaction with these transmembrane adhesion receptors and preventing their binding to proteins in the extracellular matrix and other cells. This interaction gives disintegrins their wide range of biological functions, including inhibition of platelet aggregation and antitumor activity. As a result, many studies have been conducted in an attempt to use these natural compounds as a basis for developing therapies for the treatment of various diseases. Furthermore, the FDA has approved Tirofiban and Eptifibatide as antiplatelet compounds, and they are synthesized from the structure of echistatin and barbourin, respectively. In this review, we discuss some of the main functional and structural characteristics of this class of proteins and their potential for therapeutic use.
蛇毒去整合素是一类低分子量、富含半胱氨酸的非酶蛋白，存在于蝰蛇科、响尾蛇科、穴蝰科、眼镜蛇科和游蛇科蛇类的毒液中。这类蛋白质起源于毒液中金属蛋白酶（SVMPs）的蛋白水解加工过程，而金属蛋白酶又是从编码去整合素金属蛋白酶（ADAM）分子的基因进化而来。去整合素在其结构中具有整合素识别基序，能够与这些跨膜黏附受体相互作用，阻止它们与细胞外基质中的蛋白质及其他细胞结合。这种相互作用赋予了去整合素广泛的生物学功能，包括抑制血小板聚集和抗肿瘤活性。因此，人们进行了许多研究，试图以这些天然化合物为基础开发治疗各种疾病的疗法。此外，美国食品药品监督管理局（FDA）已批准替罗非班和依替巴肽作为抗血小板化合物，它们分别是根据echistatin和barbourin的结构合成的。在这篇综述中，我们讨论了这类蛋白质的一些主要功能和结构特征及其治疗应用潜力。
