Trifluoroselenomethionine: A New Unnatural Amino Acid.
Trifluoroselenomethionine: A New Unnatural Amino Acid.
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DOI：
10.1002/cbic.201600266
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发表时间：
2016-09-15
期刊：
影响因子：
--
通讯作者：
Zeng H
中科院分区：
文献类型：
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作者：
Block E;Booker SJ;Flores-Penalba S;George GN;Gundala S;Landgraf BJ;Liu J;Lodge SN;Pushie MJ;Rozovsky S;Vattekkatte A;Yaghi R;Zeng H
以N-（叔丁氧羰基）-L-天冬氨酸叔丁酯为起始原料，经七步反应合成了一种新型非天然氨基酸三氟硒代蛋氨酸（TFSeM）。与硒代蛋氨酸（SeM）相比，TFSeM显示出增强的甲硫氨酸酶诱导的对人结肠癌衍生的HCT-116细胞的细胞毒性。这种增强活动的机制解释计算和实验研究。通过硒EXAFS和DFT计算比较TFSeM和SeM，表明它们在光谱和结构上非常相似。尽管如此，当蛋白质GB 1的两种不同变体在E.使用TFSeM和甲硫氨酸（Met）以9：1的摩尔比对大肠杆菌甲硫氨酸营养缺陷型细胞系进行的研究中，令人惊讶地发现，85%的蛋白质由SeM组成，即使没有添加SeM，这意味着TFSeM中三氟甲基的损失。TFSeM再循环为SeM是由E.大肠杆菌提取物。然而，TFSeM不是E.大肠杆菌蛋氨酸腺苷转移酶。
Trifluoroselenomethionine (TFSeM), a novel non-natural amino acid, was synthesized in seven steps from N-(tert-butoxycarbonyl)-L-aspartic acid tert-butyl ester. TFSeM shows enhanced methioninase-induced cytotoxicity toward human colon cancer derived HCT-116 cells compared to selenomethionine (SeM). Mechanistic explanations for this enhanced activity are computationally and experimentally examined. Comparison of TFSeM and SeM by selenium EXAFS and DFT calculations showed them to be spectroscopically and structurally very similar. None-the-less, when two different variants of the protein GB1 were expressed in an E. coli methionine auxotroph cell line using TFSeM and methionine (Met) in a 9:1 molar ratio, it was found that, surprisingly, 85% of the proteins were composed of SeM, even though no SeM had been added, implying loss of the trifluoromethyl group from TFSeM. The recycling of TFSeM to SeM is enzymatically catalyzed by E. coli extracts. However, TFSeM is not a substrate of E. coli methionine adenosyltransferase.