© 2004 by Oxford University Press
Analysis of distamycin A binding to UV-damaged DNA
1 Division of Chemistry, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531, Japan, 2 Japan Biological Information Research Center (JBIRC), Japan Biological Informatics Consortium (JBIC), 2-41-6 Aomi, Koto-ku, Tokyo 135-0064, Japan and Biomolecular Engineering Research Institute 6-2-3 Furuedai, Suita, Osaka 565-0874, Japan, 3 Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan, 4 Division of Biofunctional Molecules, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan, 5 Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa Oiwakecho, Sakyo-ku, Kyoto 606-8502, Japan
We have found that distamycin A can bind to DNA duplexes containing the (6–4) photoproduct, one of the major UV lesions in DNA, in spite of the changes caused by photoproduct formation in the chemical structure of the base moiety and the local tertiary structure of the duplex. Distamycin binding was analyzed in detail using 14-mer duplexes. Curve fitting of the CD titration data and induced CD difference Spectra revelaed that the binding stoichiometry changed from 1:1 to 2:1 with the photoproduct formation. Melting curves of the drug-DNA complexes also supported this stoichiometry.