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来自蛇毒的利钠肽药物先导物。

Natriuretic peptide drug leads from snake venom.

机构信息

Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.

出版信息

Toxicon. 2012 Mar 15;59(4):434-45. doi: 10.1016/j.toxicon.2010.12.001. Epub 2010 Dec 10.

Abstract

Natriuretic peptides are body fluid volume modulators, termed natriuretic peptides due to a role in natriuresis and diuresis. The three mammalian NPs, atrial natriuretic peptide (ANP), brain or b-type natriuretic peptide (BNP) and c-type natriuretic peptide (CNP), have been extensively investigated for their use as therapeutic agents for the treatment of cardiovascular diseases. Although effective, short half-lives and renal side effects limit their use. In approximately 30 years of research, NPs have been discovered in many vertebrates including mammals, amphibians, reptiles and fish, with plants and, more recently, bacteria also being found to possess NPs. Reptiles have produced some of the more interesting NPs, with dendroaspis natriuretic peptide (DNP), which was isolated from the venom of the green mamba (Dendroaspis angusticeps), having greater potency and increased stability as compared to the mammalian family members, and taipan natriuretic peptide c (TNPc), which was isolated from the venom of the inland taipan (Oxyuranus microlepidotus) displaying similar activity to ANP and DNP at rat natriuretic peptide receptor A. Although promising, more research is required in this field to develop therapeutics that overcome receptor-mediated clearance, and potential toxicity issues. This review investigates the use of snake venom NPs as therapeutic drug leads.

摘要

利钠肽是体液容量调节剂,因其在利钠和利尿中的作用而被称为利钠肽。三种哺乳动物 NP,即心房利钠肽(ANP)、脑或 B 型利钠肽(BNP)和 C 型利钠肽(CNP),因其作为心血管疾病治疗药物的用途而得到广泛研究。尽管有效,但半衰期短和肾脏副作用限制了它们的使用。在大约 30 年的研究中,NP 已在许多脊椎动物中被发现,包括哺乳动物、两栖动物、爬行动物和鱼类,最近还发现植物和细菌也具有 NP。爬行动物产生了一些更有趣的 NP,其中从绿曼巴蛇(Dendroaspis angusticeps)毒液中分离出的树眼镜蛇利钠肽(DNP)与哺乳动物家族成员相比具有更高的效力和稳定性,而从内陆太攀蛇(Oxyuranus microlepidotus)毒液中分离出的太攀蛇利钠肽 c(TNPc)在大鼠利钠肽受体 A 上显示出与 ANP 和 DNP 相似的活性。尽管有希望,但该领域还需要更多的研究来开发克服受体介导清除和潜在毒性问题的治疗方法。本综述研究了蛇毒 NP 作为治疗药物的先导。

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