Structure of the first parallel DNA quadruplex-drug complex

被引:197
作者
Clark, GR [1 ]
Pytel, PD
Squire, CJ
Neidle, S
机构
[1] Univ Auckland, Dept Chem, Auckland 1, New Zealand
[2] Univ London, Sch Pharm, Canc Res UK Biomol Struct Grp, London WC1N 1AX, England
关键词
D O I
10.1021/ja0297988
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The first crystal structure of a drug (daunomycin) bound to a parallel-stranded intermolecular telomeric G4 quadruplex (d(TGGGGT)4) has been determined to high resolution. A planar assemblage of three daunomycin molecules stacks onto the 5′ end of the G4 column, with the daunosamine substituents occupying three of the four quadruplex grooves. The surface area of the terminal G-quartet in this parallel DNA quadruplex, presently occupied by three daunomycins, is sufficiently large that it could easily accommodate other potential telomerase inhibitors such as substituted porphyrins or telomestatin. Copyright © 2003 American Chemical Society.
引用
收藏
页码:4066 / 4067
页数:2
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