Taxol-DNA interactions: fluorescence and CD studies of DNA groove binding properties of taxol

被引:114
作者
Krishna, AG [1 ]
Kumar, DV
Khan, BM
Rawal, SK
Ganesh, KN
机构
[1] Natl Chem Lab, Div Organ Chem S, Pune 411008, Maharashtra, India
[2] Natl Chem Lab, Div Plant Tiss Cult, Pune 411008, Maharashtra, India
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS | 1998年 / 1381卷 / 01期
关键词
taxol; fluorescence; CAgC; DNA binding; REES; conformation;
D O I
10.1016/S0304-4165(98)00019-1
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
Taxol is perhaps the most successful drug used for the treatment of various cancers. Comprehensive literature accumulated on therapeutics of the drug has indicated numerous side effects. In this paper, by use of fluorescence spectroscopy, it is shown that taxol binds to DNA with an affinity constant (K-a) of 1.08 X 10(7) M-1. This binding is accompanied by a large 'red edge excitation shift' (REES) of fluorescence emission maximum in taxol-DNA complex. The results point to an interaction of taxol with its core eight-membered ring in the DNA groove and the three phenyl rings projecting away from the DNA. The drug encompasses about two base pairs of DNA upon binding to it. Systematic studies with taxol analogues confirms such a mode of binding. These interesting findings on hitherto unknown taxol-DNA interactions may have clinical implications in view of its large number of side effects and pharmacokinetics. (C) 1998 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:104 / 112
页数:9
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