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从印度尼西亚巴厘岛各种有毒海洋芋螺的芋螺毒素中筛选潜在的神经元药物先导物。

Selecting Potential Neuronal Drug Leads from Conotoxins of Various Venomous Marine Cone Snails in Bali, Indonesia.

作者信息

Sudewi Anak A R, Susilawathi Ni M, Mahardika Bayu K, Mahendra Agung N, Pharmawati Made, Phuong Mark A, Mahardika Gusti N

机构信息

Neurology Department of the Faculty of Medicine and Pharmacology Department of the Faculty of Medicine, Udayana University, Jl. Sudirman, Denpasar 80226, Bali, Indonesia.

The Animal Biomedical and Molecular Biology Laboratory, Udayana University of Bali, Jl. Sesetan-Markisa 6, Denpasar 80223, Bali, Indonesia.

出版信息

ACS Omega. 2019 Nov 6;4(21):19483-19490. doi: 10.1021/acsomega.9b03122. eCollection 2019 Nov 19.

Abstract

Many conotoxins, natural peptides of marine cone snails, have been identified to target neurons. Here, we provide data on pharmacological families of the conotoxins of 11 species of cone snails collected in Bali. The identified definitive pharmacological families possibly targeting neuronal tissues were α (alpha), ι (iota), κ (kappa), and ρ (rho). These classes shall target nicotinic acetylcholine receptors, voltage-gated Na channels, voltage-gated K channels, and α1-adrenoceptors, respectively. The VI/VII-O3 conotoxins might be prospected as an inhibitor of -methyl-d-aspartate. Con-ikot-ikot could be applied as an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor blocker medicine. The definitive pharmacology classes of conotoxins as well as those yet to be elucidated need to be further established and verified.

摘要

许多芋螺毒素,即海产芋螺的天然肽,已被确定可作用于神经元。在此,我们提供了在巴厘岛采集的11种芋螺的芋螺毒素药理学家族的数据。已确定的可能作用于神经组织的明确药理学家族为α(阿尔法)、ι(约塔)、κ(卡帕)和ρ(柔)。这些类别分别作用于烟碱型乙酰胆碱受体、电压门控钠通道、电压门控钾通道和α1肾上腺素能受体。VI/VII - O3芋螺毒素有望成为N - 甲基 - D - 天冬氨酸的抑制剂。芋螺毒素Con - ikot - ikot可作为α - 氨基 - 3 - 羟基 - 5 - 甲基 - 4 - 异恶唑丙酸受体阻断药物。芋螺毒素的明确药理学类别以及那些有待阐明的类别都需要进一步确立和验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a79/6868881/5d5b5ade2d72/ao9b03122_0001.jpg

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