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通过高效液相色谱-质谱联用技术分析芋螺毒液肽谱:种内变异的新见解

Conus ventricosus venom peptides profiling by HPLC-MS: a new insight in the intraspecific variation.

作者信息

Romeo Cristina, Di Francesco Laura, Oliverio Marco, Palazzo Paola, Massilia Gabriella Raybaudi, Ascenzi Paolo, Polticelli Fabio, Schininà Maria Eugenia

机构信息

Consorzio Interuniversitario Istituto Nazionale Biostrutture e Biosistemi, Rome, Italy.

出版信息

J Sep Sci. 2008 Feb;31(3):488-98. doi: 10.1002/jssc.200700448.

DOI:10.1002/jssc.200700448
PMID:18266261
Abstract

Conus is a genus of predatory marine gastropods that poison the prey with a complex mixture of compounds active on muscle and nerve cells. An individual cone snail's venom contains a mixture of pharmacological agents, mostly short, structurally constrained peptides. This study is focused on the composition of the venom employed by Conus ventricosus Gmelin, 1791, a worm-hunting cone snail living in the Mediterranean Sea. For this purpose, LC coupled to MS techniques has been successfully used to establish qualitative and quantitative differences in conopeptides from minute amounts of venom ducts. We were able to prove variability in the venom conopeptide complement, possibly related to different trophic habits of the species in the Mediterranean Sea. Moreover, the information-rich MS techniques enabled us to identify two novel C. ventricosus peptides, here named Conotoxin-Vn and -Conotoxin-Vn. On the basis of the structural data collected so far, we suggest that Conotoxin-Vn is a conopeptide belonging to the -family that recognizes calcium channels through a specific pharmacophore. Similarly, molecular modeling data suggest that -Conotoxin-Vn should represent a competitive antagonist of neuronal nicotinic acetylcholine receptors (nAChRs).

摘要

芋螺属是一类肉食性海洋腹足纲动物,它们用一种对肌肉和神经细胞有活性的复杂化合物混合物毒害猎物。单个芋螺的毒液含有多种药理剂,大多是结构受限的短肽。本研究聚焦于1791年命名的腹突芋螺(Conus ventricosus Gmelin)的毒液成分,它是一种生活在地中海的捕食蠕虫的芋螺。为此,液相色谱与质谱联用技术已成功用于确定微量毒液管中芋螺肽的定性和定量差异。我们能够证明毒液芋螺肽成分的变异性,这可能与该物种在地中海的不同食性有关。此外,信息丰富的质谱技术使我们能够鉴定出两种新的腹突芋螺肽,在此命名为芋螺毒素-Vn和-芋螺毒素-Vn。根据目前收集到的结构数据,我们认为芋螺毒素-Vn是一种属于-家族的芋螺肽,它通过特定的药效基团识别钙通道。同样,分子模拟数据表明-芋螺毒素-Vn应该是神经元烟碱型乙酰胆碱受体(nAChRs)的竞争性拮抗剂。

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