Interaction of Topotecan, DNA Topoisomerase I Inhibitor, with Double-stranded Polydeoxyribonucleotides. 3. Binding at the Minor Groove

Abstract

Interaction of topotecan (TPT) with calf thymus DNA, coliphage T4 DNA, and poly(dGdC) · poly(dG-dC) was studied by optical (linear flow dichroism, UV-vis spectroscopy) and quantum chemical methods. The linear dichroism signal of TPT bound to DNA was shown to have positive sign in the range 260–295 nm. This means that the plane of quinoline fragment (rings A and B) of TPT forms an angle less than 54° with the long axis of DNA, and hence the TPT molecule cannot intercalate between DNA base pairs. TPT was established to bind to calf thymus DNA as readily as to coliphage T4 DNA whose cytosines in the major groove were all glycosylated at the 5th position. Consequently, the DNA major groove does not participate in TPT binding. TPT molecule was shown to compete with distamycin for binding sites in the minor groove of DNA and poly(dG-dC) · poly(dG-dC). Thus, it was demonstrated for the first time that TPT binds to DNA at its minor groove.

DOI: 10.1023/A:1016067515071

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Cite this paper

@article{Streltsov2002InteractionOT, title={Interaction of Topotecan, DNA Topoisomerase I Inhibitor, with Double-stranded Polydeoxyribonucleotides. 3. Binding at the Minor Groove}, author={Sergey A Strel'tsov and Andrey L. Mikheikin and S. L. Grokhovsky and Vladimir A Oleinikov and A. L. Zhuze}, journal={Molecular Biology}, year={2002}, volume={36}, pages={400-411} }