Interaction of a spin-labeled adenine-acridine conjugate with a DNA duplex containing an abasic site model

被引：22

作者：

Thomas, F ^{[1
]}

Michon, J ^{[1
]}

Lhomme, J ^{[1
]}

机构：

[1] Univ Grenoble 1, Etud Dynam & Struct Select Lab, CNRS, UMR 5616, F-38041 Grenoble 9, France

来源：

BIOCHEMISTRY | 1999年 / 38卷 / 06期

关键词：

D O I：

10.1021/bi981770e

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：

The abasic sire is a common lesion in DNA that is also formed as an intermediate in the base excision repair of damaged bases. We have previously reported the adenine-acridine conjugate 1 that was designed to bind to the abasic site and interfere with the repair process. High-field NMR had shown that 1 forms specific complexes with a DNA duplex containing an apurinic abasic site model. We report here the dynamics of the interaction of the nitroxide-labeled analogue 3 of the conjugate 1 with the same apurinic oligonucleotide and with the parent unmodified, duplex. Identical study of the labeled acridine subunit 5 used as a reference is also reported. In the presence of the apurinic duplex and depending on the concentrations and drug ratios, three species are observed: the radical "free in solution", the "intercalation" complex characterized by its similarity to that observed in the presence of the parent unmodified duplex, and the "abasic-site-specific" complex which is the sole species visible at low drug ratios. The experimental data reinforced by molecular modeling of the complex and theoretical calculation of correlation times suggest (i) the most immobilized form corresponds to that observed by NMR and (ii) complexation of the drug is little or not modified by the spin-label. We also show that the abasic site constitutes a binding site for the. propylaminoacridine intercalator 5.

引用

页码：1930 / 1937

页数：8

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