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国际上被誉为“海洋药物宝库”的芋螺毒素(CTx),具有特异结合动物体内各种离子通道和受体的特殊功能。其中的α*-芋螺毒素(α*-CTxs)能特异性地作用于乙酰胆碱受体(n ACh Rs),对其亚型具有极高的选择性阻断活性。不同的亚基组合形成的各种乙酰胆碱受体亚型,在正常健康状态下和多种疾病状态下起着很重要的生理和病理学功能,这些功能至今尚不很清楚,因而发现和开发各种亚型的选择性分子探针,如α*-CTxs将有助于阐释各个亚型的精细结构和功能。深入研究特异阻断乙酰胆碱受体不同亚型的α*-CTxs的结构与功能,及其与受体相互作用的机理具有很重要的科学意义,将有助于研发出与n ACh Rs相关的多种疑难杂症的治疗药物,包括神经痛、癌症化疗、成瘾、痴呆、重症肌无力、精神分裂症、癫痫、乳腺癌、肺癌、脑脊髓炎,以及其他神经疾病等。近年来,我们实验室经过大量筛选研究,鉴定出5个海南产新颖α*-芋螺毒素,对它们的人工合成、三维结构、作用靶点、与受体相互作用机制、药理药效等进行了深入的研究。现对上述特异阻断乙酰胆碱受体不同亚型的5个海南产α*-芋螺毒素的研究进展和应用前景进行综述。
The conotoxin (CTx), internationally recognized as the “Treasure of Marine Drugs”, has the specific function of specifically binding to various ion channels and receptors in animals. Among them, α * -conotoxin (α * -CTxs) can specifically act on acetylcholine receptor (nAChRs) and has a very high selective blocking activity on its subtype. The various subtypes of acetylcholine receptor subtypes formed by the combination of different subunits play a very important physiological and pathological function under normal conditions and in a variety of disease states and these functions are not yet known so far, Selective molecular probes of subtypes, such as α * -CTxs, will help elucidate the fine structure and function of each subtype. In-depth study of the structure and function of α * -CTxs specifically blocking different subtypes of acetylcholine receptor and its mechanism of interaction with receptors is of great scientific significance and will contribute to the development of more nACh Rs-related The treatment of intractable diseases, including neuralgia, cancer chemotherapy, addiction, dementia, myasthenia gravis, schizophrenia, epilepsy, breast cancer, lung cancer, encephalomyelitis, and other neurological diseases. In recent years, our laboratory through a large number of screening studies identified five new α - conotoxin production in Hainan, their synthetic, three-dimensional structure, the role of the target, the interaction mechanism with the receptor, pharmacological effects such as In-depth research. The above research progress and application prospect of five α - conotoxins producing Hainan that specifically block different subtypes of acetylcholine receptors are reviewed.