Bis-3-chloropiperidines containing bridging lysine linkers: Influence of side chain structure on DNA alkylating activity
Bis-3-chloropiperidines containing bridging lysine linkers: Influence of side chain structure on DNA alkylating activity
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DOI：
10.1016/j.bmc.2015.01.050
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发表时间：
2015-03-15
影响因子：
3.5
通讯作者：
Gatto, Barbara
中科院分区：
文献类型：
--
作者：
Zuravka, Ivonne;Roesmann, Rolf;Gatto, Barbara
采用双向合成策略合成了一系列含赖氨酸连接体的双-3-氯哌啶作为DNA烷基化模型化合物。这些新型的胡椒碱芥菜剂对核酸的烷基化特性进行了评估，并显示出对鸟嘌呤残基有强烈偏好的烷基化和切割DNA。我们的研究表明，在赖氨酸连接体侧链上引入芳香基团对DNA烷基化活性有影响。ESI质谱分析证实了反应性氮铱离子的形成。总的来说，结果证实了我们最近提出的双-3-氯哌啶的反应机理。(C) 2015 Elsevier Ltd.版权所有。
A series of bis-3-chloropiperidines containing lysine linkers was synthesised as DNA alkylating model compounds by using a bidirectional synthetic strategy. These novel piperidine mustard based agents have been evaluated for their alkylating properties towards nucleic acids and were shown to alkylate and cleave DNA with strong preference for guanine residues. Our studies reveal that the introduction of aromatic groups in the side chain of the lysine linker has an impact on DNA alkylating activity. Analysis by ESI mass spectrometry enabled the verification of the reactive aziridinium ion formation. Overall, the results confirm our recently proposed reaction mechanism of bis-3-chloropiperidines. (C) 2015 Elsevier Ltd. All rights reserved.