Characterization of distamycin A binding to damaged DNA.
We previously reported that distamycin A, a natural antibiotic known as a minor groove binder, could bind to DNA duplexes containing the (6-4) photoproduct formed at its target site, whereas the binding was not observed for duplexes containing the cis-syn cyclobutane pyrimidine dimer in the same sequence context. In this study, we have further analyzed the binding of this drug to lesion-containing duplexes to elucidate its damaged-DNA recognition mechanism. Surface plasmon resonance measurements using various types of DNA showed that distamycin A could bind to several types of lesion-containing DNA. Curve fitting of the CD titration data revealed that the complex formation occurred with K(d) values around 10(-6) and a stoichiometry of 1:1. The results obtained in this study suggested that distamycin A binds to damaged DNA in the same way as to the normal target site, by recognizing the chemical structure of the minor groove.
Inase-Hashimoto
Aki
A
Division of Chemistry, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531, Japan.
Yoshikawa
Shinya
S
Kawasaki
Yusuke
Y
Kodama
Takashi S
TS
Iwai
Shigenori
S
D001665:Binding Sites; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism* / Q000648:ultrastructure; D004249:DNA Damage; D004214:Distamycins / Q000493:pharmacokinetics*; D020349:Surface Plasmon Resonance; D017186:Titrimetry
D004214:Distamycins; C030000:stallimycin; D004247:DNA