Department of Medicine, National University of Singapore, Singapore.
Protein Science Laboratory, Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore.
Semin Thromb Hemost. 2018 Oct;44(7):691-706. doi: 10.1055/s-0038-1661384. Epub 2018 Jun 28.
Venomous and hematophagous animals use their venom or saliva for survival, to obtain food, and for self-defense. Venom and saliva from these animals are cocktails of bioactive molecules primarily composed of proteins and peptides. These molecules are called toxins because they cause unwanted consequences on prey. They exhibit unique, diverse, and specific biological activities that perturb normal physiological processes of their prey and host. However, the potential of toxins as inspirations for the development of therapeutic agents or pharmacological tools has also long been recognized. In addition to their small size, the exquisite selectivity and structural stability of toxins make them attractive as starting molecule in the development of therapeutic and diagnostic agents. Drug discovery and development from venomous and hematophagous animals against cardiovascular diseases have been particularly successful. Some of the notable success include antihypertensive (captopril and enalapril) and antiplatelet agents (tirofiban and eptifibatide), as well as anticoagulants (lepirudin and bivalirudin). Highlighted in this review are many venom or saliva-derived cardiovascular-active proteins and peptides of therapeutic interest, including those that are currently in preclinical stages and those that have been approved by FDA and currently in the market. The authors attempt to summarize their structure, function, mechanism of action, and development with respect to cardiovascular diseases.
有毒和吸血动物利用它们的毒液或唾液来生存、获取食物和自卫。这些动物的毒液和唾液是由生物活性分子组成的混合物，主要由蛋白质和肽组成。这些分子被称为毒素，因为它们会对猎物造成不必要的后果。它们表现出独特、多样和特定的生物活性，扰乱了猎物和宿主的正常生理过程。然而，毒素作为治疗剂或药理学工具开发的灵感来源的潜力也早已被认识到。除了它们的体积小，毒素的精致选择性和结构稳定性使它们成为治疗和诊断剂开发的有吸引力的起始分子。从有毒和吸血动物中针对心血管疾病的药物发现和开发特别成功。一些显著的成功包括抗高血压（卡托普利和依那普利）和抗血小板药物（替罗非班和依替巴肽）以及抗凝剂（来匹卢定和比伐卢定）。本文重点介绍了许多具有治疗价值的心血管活性的毒液或唾液衍生的蛋白质和肽，包括那些处于临床前阶段的以及那些已经获得 FDA 批准并在市场上的。作者试图总结它们在心血管疾病方面的结构、功能、作用机制和开发情况。
