Catalysis of the CC-1065 and duocarmycin DNA alkylation reaction: DNA binding induced conformational change in the agent results in activation
Catalysis of the CC-1065 and duocarmycin DNA alkylation reaction: DNA binding induced conformational change in the agent results in activation
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DOI：
10.1016/s0968-0896(96)00238-6
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发表时间：
1997-02-01
影响因子：
3.5
通讯作者：
Garbaccio, RM
中科院分区：
文献类型：
--
作者：
Boger, DL;Garbaccio, RM
总结了许多间接观察结果，表明 CC-1065 和多卡霉素 DNA 烷基化反应的速率加速部分源自试剂中 DNA 结合诱导的构象变化，这大大增加了它们的固有反应性。我们认为该试剂的基态不稳定是由于连接 N2 酰胺中结合诱导的扭曲造成的，并且需要刚性延伸的 N2 酰胺取代基，它会破坏插烯酰胺的稳定性并激活试剂进行 DNA 烷基化。 (C) 1997，爱思唯尔科学有限公司。
A number of indirect observations are summarized that suggest the rate acceleration for the CC-1065 and duocarmycin DNA alkylation reaction is derived in part from a DNA binding-induced conformational change in the agents which substantially increases their inherent reactivity. This ground-state destabilization of the agent, which we suggest results from a binding-induced twist in the linking N2 amide and requires a rigid extended N2 amide substituent, disrupts the vinylogous amide stabilization and activates the agents for DNA alkylation. (C) 1997, Elsevier Science Ltd.