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一种基于两种分泌毒素的海洋环节动物之间比较转录组学的药物发现方法:以及。 (注:原文中“and.”表述不完整,可能影响准确理解。)

A drug discovery approach based on comparative transcriptomics between two toxin-secreting marine annelids: and .

作者信息

Moutinho Cabral Inês, Madeira Carolina, Grosso Ana R, Costa Pedro M

机构信息

Associate Laboratory i4HB - Institute for Health and Bioeconomy, NOVA School of Science and Technology, NOVA University of Lisbon, 2829-516 Caparica, Portugal.

UCIBIO - Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, NOVA University of Lisbon, 2829-516 Caparica, Portugal.

出版信息

Mol Omics. 2022 Sep 26;18(8):731-744. doi: 10.1039/d2mo00138a.

Abstract

Most animal toxins evolved to interact with specific molecular targets, which makes them highly-prized bioactives for drug development. Marine toxins, in particular, due to their wide chemical diversity, offer a new range of possibilities, a few of which have already been translated into approved drugs. and are sympatric Polychaeta with distinct ecology and behavior suspected to secrete toxins that evolved to interact with distinct molecular targets, thus with differential selectivity and potential applications in drug discovery. Comparative transcriptomics revealed that while 's venom apparatus is localized in the proboscis and neurotoxins are secreted to overtake prey, secretes fewer and less specific toxins that are seemingly a defense. Human interactome-directed analysis unraveled novel toxins and other bioactives with potential biomedical applications, like proteins from 's venom that can regulate apoptosis, whereas yielded proteins that may control inflammation and cell proliferation in humans. Omics and bioinformatics appear to be powerful tools for marine bioprospecting and drug discovery, enabling molecular mining through transcriptomes of non-model organisms and link their ecology and physiology with protein's specificity and bioreactivity. Interactome-directed analysis against the human proteome seems an efficient alternative to the design of synthetic drugs.

摘要

大多数动物毒素进化为与特定分子靶点相互作用,这使其成为药物开发中备受青睐的生物活性物质。特别是海洋毒素,由于其广泛的化学多样性,提供了一系列新的可能性,其中一些已转化为获批药物。[物种名称1]和[物种名称2]是同域分布的多毛纲动物,具有不同的生态和行为,疑似分泌与不同分子靶点相互作用的毒素,因此具有不同的选择性和在药物发现中的潜在应用。比较转录组学表明,[物种名称1]的毒液器官位于吻部,神经毒素分泌出来以制服猎物,而[物种名称2]分泌的毒素较少且特异性较低,似乎是一种防御手段。针对人类相互作用组的分析揭示了具有潜在生物医学应用的新型毒素和其他生物活性物质,例如来自[物种名称1]毒液的可调节细胞凋亡的蛋白质,而[物种名称2]产生的蛋白质可能控制人类的炎症和细胞增殖。组学和生物信息学似乎是海洋生物勘探和药物发现的强大工具,能够通过非模式生物的转录组进行分子挖掘,并将它们的生态和生理与蛋白质的特异性和生物反应性联系起来。针对人类蛋白质组的相互作用组导向分析似乎是合成药物设计的有效替代方法。

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