氯毒素 | 163515-35-3

• 物质功能分类: 生物化工 - 提取物 - 动物提取物
• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 中文名称: 氯毒素
• 中文别名: 氯代毒素
• 英文名称: H-D-Met-D-Cys(1)-Met-Pro-D-Cys(2)-Phe-Thr-Thr-Asp-His-D-Gln-Met-Ala-Arg-Lys-DL-Cys(3)-Asp-Asp-Cys(1)-Cys(4)-Gly-Gly-D-Lys-Gly-D-Arg-Gly-D-Lys-D-Cys(2)-D-Tyr-Gly-Pro-D-Gln-DL-Cys(3)-D-Leu-Cys(4)-Arg-NH2
• 英文别名: 2-[(1R,4R,5aR,8aR,9S,12S,17aS,18S,20aS,21S,24S,27S,30S,33S,36S,39R,42S,45S,48S,51S,62R,65S,74R,77S,80R,86R,92R)-51,80,92-tris(4-aminobutyl)-5a-[[(2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl]carbamoyl]-9-[[(2R)-2-amino-4-methylsulfanylbutanoyl]amino]-39,62-bis(3-amino-3-oxopropyl)-24-benzyl-48,86-bis(3-carbamimidamidopropyl)-20a,33-bis(carboxymethyl)-27,30-bis[(1R)-1-hydroxyethyl]-74-[(4-hydroxyphenyl)methyl]-36-(1H-imidazol-4-ylmethyl)-45-methyl-8a-(2-methylpropyl)-12,42-bis(2-methylsulfanylethyl)-a,3,7a,10,10a,13,15a,18a,19,21a,22,25,28,31,34,37,40,43,46,49,52,61,64,70,73,76,79,82,85,88,91,94,97-tritriacontaoxo-2a,3a,6,7,12a,13a,56,57-octathia-2,6a,9a,11,14,16a,19a,20,22a,23,26,29,32,35,38,41,44,47,50,53,60,63,69,72,75,78,81,84,87,90,93,96,99-tritriacontazahexacyclo[57.41.10.84,54.421,77.014,18.065,69]docosahectan-17a-yl]acetic acid
• CAS: 163515-35-3
• 化学式: C₁₅₈H₂₄₉N₅₃O₄₇S₁₁
• 分子量: 3996.0
• InChiKey: QPAKKWCQMHUHNI-XUJKACQMSA-N

物化性质

• 溶解度：
  可溶于水性缓冲液

计算性质

• 辛醇/水分配系数(LogP)：
  -22
• 重原子数：
  269
• 可旋转键数：
  63
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  1900
• 氢给体数：
  56
• 氢受体数：
  66

安全信息

• WGK Germany：
  3

制备方法与用途

概述

氯毒素(chlorotoxin）是一种蝎毒素多肽,从以色列蝎子Leiurus quinquestraqtum分离得到，作为人体神经胶质瘤选择性靶向新药和诊断(包括级别判断)的特异标记有着巨大的应用前景。

作用机理

人脑星形细胞瘤产生一种独特的电压依赖的氯离子电流(称GCC电流,其氯离子通道称GCC通道),它在人正常细胞(包括正常的神经胶质细胞)以及非神经胶质来源的人体肿瘤细胞中均不产生,这种氯电流可以被Cl-通道抑制剂氯毒素有效抑制,并导致脑瘤细胞繁殖速度的改变,推测Cl-通道参与了星形细胞瘤生长的调控。对氯毒素敏感的GCC电流在植入的神经胶质瘤细胞中持续出现,而在相邻的正常宿主神经胶质细胞中不出现。证实这种独特的氯离子通道是神经胶质瘤所特有的。氯毒素对这种氯离子通道的选择性结合提供了一个鉴定和治疗神经胶质瘤的有效的新途径。氯毒素选择性地结合在神经胶质瘤细胞上,而人体正常组织包括脑、肾、肠等均呈现氯毒素免疫着色阴性。

应用

人体神经胶质瘤选择性靶向新药

主要参考资料

[1]曾宪春,李文鑫. 氯毒素的抗神经胶质瘤作用[J]. 生命的化学,1999,(04):49-50.

生物活性

Chlorotoxin是从雷蛇属以色列蝎子的毒液中提取的由36个氨基酸组成的肽段，具有抗癌活性。Chlorotoxin是氯离子通道 (chloride channel) 阻断剂。

靶点

Target: Chloride Channel

体外研究

Chlorotoxin (Chlorotoxin) preferentially binds to tumor cells and has been harnessed to develop an imaging agent to help visualize tumors during surgical resection. In addition, chlorotoxin has potential as a vehicle to deliver anti-cancer drugs specifically to cancer cells. Chlorotoxin is shown to bind glioma cells, but is unable to bind normal rat astrocytes and Te671, a human rhabdomyosarcoma cell line. Chlorotoxin inhibits the migration of U251MG (glioma) cells, with an IC ₅₀ of 600 nM. Chlorotoxin binds to glioma cells is specific and involves high affinity (K _d =4.2 nM) and low affinity (K _d =660 nM) binding sites.Small conductance chloride channels are shown to be potently blocked by Chlorotoxin. Chlorotoxin has been used as a general pharmacological tool to investigate the function of chloride channels.

体内研究

Chlorotoxin shows insecticidal activity on insects and other invertebrates. After the administration of I-Chlorotoxin to tumor-bearing mice, the peptides accumulated within the tumor.Chlorotoxin selectively accumulates in the brain of tumor-bearing mice with calculated brain: muscle ratios of 36.4% of injected dose/g (ID/g), as compared to 12.4%ID/g in control animals.