title: Binding of distamycin A to UV-damaged DNA.
abstract: We have found that distamycin A can bind to DNA duplexes containing the (6-4) photoproduct, one of the major UV lesions in DNA, despite the changes, caused by photoproduct formation, in both the chemical structure of the base moiety and the local tertiary structure of the helix. A 20-mer duplex containing the target site, AATT.AATT, was designed, and then one of the TT sequences was changed to the (6-4) photoproduct. Distamycin binding to the photoproduct-containing duplex was detected by CD spectroscopy, whereas specific binding did not occur when the TT site was changed to a cyclobutane pyrimidine dimer, another type of UV lesion. Distamycin binding was analyzed in detail using 14-mer duplexes. Curve fitting of the CD titration data and induced CD difference spectra revealed that the binding stoichiometry changed from 1:1 to 2:1 with photoproduct formation. Melting curves of the drug-DNA complexes also supported this stoichiometry.
authors.affiliation: Contribution from the Division of Chemistry, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Inase
authors.forename: Takashi S
authors.initials: TS
authors.lastname: Kodama
authors.forename: Jafar
authors.initials: J
authors.lastname: Sharif
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Hirohito
authors.initials: H
authors.lastname: Ayame
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiyama
authors.forename: Shigenori
authors.initials: S
authors.lastname: Iwai
mesh_terms: D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000378:metabolism* / Q000528:radiation effects*; D004249:DNA Damage; D004214:Distamycins / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D017186:Titrimetry
chemical_list: D004214:Distamycins; C030000:stallimycin; D004247:DNA