Conotoxins, isolated from the venom of carnivorous marine snails of the Conus genus, are disulfide-rich peptides and proteins with well-defined three-dimensional structures. Conotoxins’ ability to target a wide range of ion channels and receptors, including voltage- and ligand-gated ion channels, G protein-coupled receptors, monoamine transporters, and enzyme, at exquisite potency and selectivity make them valuable research and therapeutic tools. Despite their potentials, Conus venom peptides are present in limited quantities in nature and possess structural complexity that raises significant synthetic challenges for both chemical synthesis and recombinant expression. Here, we document recent advances in the expression and synthesis of conotoxins, particularly focusing on directed formation of disulfide bonds, chemical ligation techniques, and the integration of non-native functional groups. These advances can provide access to even the most complex conotoxins, accelerating conotoxin-based drug discovery and functional analysis, as well as opening new avenues for the development of drug candidates.

中文翻译：

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芋螺毒素合成和工程研究进展


从圆锥属肉食性海螺的毒液中分离出的芋螺毒素是富含二硫键的肽和蛋白质，具有明确的三维结构。芋螺毒素能够以极好的效力和选择性靶向广泛的离子通道和受体，包括电压和配体门控离子通道、G 蛋白偶联受体、单胺转运蛋白和酶，使其成为有价值的研究和治疗工具。尽管具有潜力，但圆锥毒肽在自然界中的含量有限，并且具有结构复杂性，这给化学合成和重组表达带来了重大的合成挑战。在这里，我们记录了芋螺毒素表达和合成的最新进展，特别关注二硫键的定向形成、化学连接技术和非天然官能团的整合。这些进步甚至可以提供最复杂的芋螺毒素，加速基于芋螺毒素的药物发现和功能分析，并为候选药物的开发开辟新的途径。