JBC：蜗牛毒液或可有效治疗癌症及成瘾症

  蜗牛在世界上某些地方被视为美味佳品，但它却引起了科学家的很多兴趣，近日，发表于国际杂志the Journal of Biological Chemistry上的一篇研究论文中，来自佛罗里达大西洋大学(Florida Atlantic University)的研究人员发现，锥形蜗牛毒液（Cone snail venom）或可用于治疗癌症及成瘾症。

  锥形蜗牛是深海中的一种软体动物，比如贝壳、章鱼和乌贼等软体动物往往通过毒液来捕食，研究者Frank Marí说道，这些软体动物产生的毒液可以固定住猎物，而其产生的毒液是一种具有药用特性的超级复杂的化合物；毒液的成分可以靶向性地作用于机体细胞，其可以作为一种有价值的药物来帮助治疗某些人类疾病，其中毒液中的一种组分为α-芋螺毒素，其可以靶向作用于烟碱性受体，而该受体对阿尔兹海默氏症、精神分裂症、肺癌等一系列疾病都非常重要。

  文章中，研究者收集的特殊种类的锥形蜗牛，其机体中的毒液富含α-芋螺毒素，而研究者Aldo Franco在实验室中进行研究后发现了10几种α-芋螺毒素，其中一种名为RegIIA的毒素可以潜在地阻断α3-β4-烟碱性受体，这种受体当其处于激活状态时常和肺癌及尼古丁成瘾直接相关。

  研究者随后调查了RegIIA如何同α3-β4-烟碱性受体相互作用，他们表示，本文研究为他们利用蜗牛毒液开发新型治疗癌症及成瘾症的疗法提供了新的思路，后期研究者将通过更为深入的研究来揭示蜗牛毒液的多种特性。（转化医学网360zhyx.com）

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转化医学网推荐的原文摘要：

Alanine Scan of α-Conotoxin RegIIA Reveals a Selective α3β4 Nicotinic Acetylcholine Receptor Antagonist*
JBC doi: 10.1074/jbc.M114.605592
Shiva N. Kompella‡1, Andrew Hung‡1, Richard J. Clark§, Frank Marí¶ and David J. Adams‡3
Activation of the α3β4 nicotinic acetylcholine receptor (nAChR) subtype has recently been implicated in the pathophysiology of various conditions, including development and progression of lung cancer and in nicotine addiction. As selective α3β4 nAChR antagonists, α-conotoxins are valuable tools to evaluate the functional roles of this receptor subtype. We previously reported the discovery of a new α4/7-conotoxin, RegIIA. RegIIA was isolated from Conus regius and inhibits acetylcholine (ACh)-evoked currents mediated by α3β4, α3β2, and α7 nAChR subtypes. The current study used alanine scanning mutagenesis to understand the selectivity profile of RegIIA at the α3β4 nAChR subtype. [N11A] and [N12A] RegIIA analogs exhibited 3-fold more selectivity for the α3β4 than the α3β2 nAChR subtype. We also report synthesis of [N11A,N12A]RegIIA, a selective α3β4 nAChR antagonist (IC50 of 370 nm) that could potentially be used in the treatment of lung cancer and nicotine addiction. Molecular dynamics simulations of RegIIA and [N11A,N12A]RegIIA bound to α3β4 and α3β2 suggest that destabilization of toxin contacts with residues at the principal and complementary faces of α3β2 (α3-Tyr92, Ser149, Tyr189, Cys192, and Tyr196; β2-Trp57, Arg81, and Phe119) may form the molecular basis for the selectivity shift.