1H NMR studies of selective interactions of norfloxacin with double-stranded DNA.
The interaction of the antibiotic drug norfloxacin with double-stranded DNA containing interior 5'-CpG-3', 5'-GpC-3', and 5'-GpG-3' steps was studied by 1H NMR. The drug is in fast exchange on the NMR timescale. A highly selective broadening of the imino proton resonances assigned to central CpG steps was observed after addition of drug, indicating an intercalation-like interaction. DNA sequences with central CpG steps also displayed broadening of non-hydrogen-bonded cytosine amino protons in the major groove upon addition of norfloxacin. Furthermore, a sequence-independent selective broadening of the adenine H2 resonance and an upfield shift of the guanine amino proton resonance, both protons located in the minor groove, was observed. Two-dimensional-NOESY spectra showed that no significant structural changes were induced in the DNA by the drug. The results suggest that the planar two-ring system of norfloxacin partially intercalates into CpG steps and that the drug also exhibits non-specific groove binding.
Sandström
Karin
K
Department of Biochemistry and Biophysics, Arrhenius Laboratory, Stockholm University, S-106 91, Stockholm, Sweden.
Wärmländer
Sebastian
S
Leijon
Mikael
M
Gräslund
Astrid
A
D000890:Anti-Infective Agents / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D003903:Deuterium; D020862:GC Rich Sequence; D009643:Norfloxacin / Q000737:chemistry* / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular
D000890:Anti-Infective Agents; D004247:DNA; D003903:Deuterium; D009643:Norfloxacin