Catalysis of the CC-1065 and duocarmycin DNA alkylation reaction: DNA binding induced conformational change in the agent results in activation

被引：95

作者：

Boger, DL ^{[1
]}

Garbaccio, RM ^{[1
]}

机构：

[1] Scripps Res Inst, DEPT CHEM, LA JOLLA, CA 92037 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 1997年 / 5卷 / 02期

关键词：

D O I：

10.1016/S0968-0896(96)00238-6

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

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页码：263 / 276

页数：14

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