Metal Cation Complexation and Activation of Reversed CPyI Analogues of CC-1065 and Duocarmycin SA: Partitioning the Effects of Binding and Catalysis

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• 作者：David A. Ellis ; Scott E. Wolkenberg ; and Dale L. Boger
• 刊名：Journal of the American Chemical Society
• 出版年：2001
• 出版时间：September 26, 2001
• 年：2001
• 卷：123
• 期：38
• 页码：9299 - 9306
• 全文大小：214K
• 年卷期：v.123,no.38(September 26, 2001)
• ISSN：1520-5126

文摘

The synthesis and examination of a novel class of reversed CPyI analogues of CC-1065 and theduocarmycins are described. Capable of a unique metal cation activation of DNA alkylation, these agentsallowed the effects of the DNA binding domain (10⁴-fold increase in DNA alkylation rate and efficiency) tobe partitioned into two components: that derived from enhanced DNA binding affinity and selectivity (10-80-fold) and that derived from a contribution to catalysis (250-5000-fold). In addition, the reversed enantiomericselectivity of these sequence selective DNA alkylating agents provides further strong support for a previouslydisclosed model where it is the noncovalent binding selectivity of the compounds, and not the alkylationsubunit or the source of catalysis, that controls the DNA alkylation selectivity.