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芋螺肽——丰富的药物宝库。

Conus peptides--a rich pharmaceutical treasure.

作者信息

Wang Cheng-Zhong, Chi Cheng-Wu

机构信息

Institute of Biochemistry and Cell Biology, Shanghai Institute of Biological Sciences, the Chinese Academy of Sciences, Shanghai 200031, China.

出版信息

Acta Biochim Biophys Sin (Shanghai). 2004 Nov;36(11):713-23. doi: 10.1093/abbs/36.11.713.

Abstract

Marine predatory cone snails (genus Conus) with over 500 species represent what is arguably the largest single genus of marine animals alive today. All Conus are venomous and utilize a complex mixture of Conus peptides to capture their preys and for other biological purposes. Each component of Conus peptides selectively targets a specific subtype of ion channels, neurotransmitter receptors or transporters. Owing to their diversity, more than 50,000 distinct active peptides are theoretically estimated in Conus venoms. These diversified toxins are generally categorized into several superfamilies and/or families based on their characteristic arrangements of cysteine residues and pharmacological actions. Some mechanisms underlying the remarkable diversity of Conus peptides have been postulated: the distinctive gene structure, gene duplication and/or allelic selection, genus speciation, and sophisticated expression pattern and post-translational modification of these peptides. Due to their highly pharmacological potency and target selectivity, Conus peptides have attracted extensive attention with their potentials to be developed as new research tools in neuroscience field and as novel medications in clinic for pain, epilepsy and other neuropathic disorders. Several instructive lessons for our drug development could be also learnt from these neuropharmacological "expertises". Conus peptides comprise a rich resource for neuropharmacologists, and most of them await to be explored.

摘要

海洋食肉芋螺(芋螺属)有500多个物种,可说是现存最大的海洋动物单属。所有芋螺都有毒,利用芋螺肽的复杂混合物来捕获猎物并用于其他生物学目的。芋螺肽的每个成分都选择性地作用于离子通道、神经递质受体或转运体的特定亚型。由于其多样性,理论上估计芋螺毒液中有超过50000种不同的活性肽。这些多样化的毒素通常根据其半胱氨酸残基的特征排列和药理作用分为几个超家族和/或家族。关于芋螺肽显著多样性的一些潜在机制已被提出:独特的基因结构、基因复制和/或等位基因选择、属物种形成,以及这些肽复杂的表达模式和翻译后修饰。由于其高度的药理活性和靶点选择性,芋螺肽因其有潜力被开发为神经科学领域的新研究工具以及临床上治疗疼痛、癫痫和其他神经疾病的新型药物而备受关注。我们还可以从这些神经药理学“专长”中学到一些对药物开发有指导意义的经验。芋螺肽为神经药理学家提供了丰富的资源,其中大多数有待探索。

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