NMR studies of chromomycin A3 interaction with DNA.
The binding of chromomycin A3 to calf thymus DNA and poly(dG-dC) has been studied by 13C and 1H NMR with emphasis on the mode of binding, the role of Mg2+, and pH effects. The most prominent changes in the DNA base pair 13C NMR resonances upon complexation with chromomycin were observed for G and C bases, consistent with the G-C preference exhibited by this compound. Comparison of the 13C spectrum of DNA-bound chromomycin A3 with that of DNA-bound actinomycin D, a known intercalator, showed many similarities in the base pair resonances. This suggested the possibility that chromomycin A3 binds via an intercalative mechanism. 1H NMR studies in the imino proton, low-field region of the spectrum provided additional evidence in support of this binding mode. In the low-field spectrum of chromomycin A3 bound to calf thymus DNA, a small shoulder was observed on the upfield side of the G-C imino proton peak. Similarly, in the chromomycin A3 complex with poly(dG-dC), a well-resolved peak was found upfield from the G-C imino proton peak. These results are expected for ligands that bind by intercalation. Furthermore, in both the calf thymus and poly(dG-dC) drug complexes (in the presence of Mg2+) a broad peak was also present downfield (approximately 16 ppm from TSP) from the DNA imino protons. This was attributed to the C-9 phenolic hydroxyl proton on the chromomycin chromophore. Visible absorbance spectra at different pH values showed that the role of Mg2+ in the binding of chromomycin A3 to DNA is more than simple neutralization of the drug's anionic change.
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E
Berman
S C
SC
Brown
T L
TL
James
R H
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Shafer
D000818:Animals; D006690:Bisbenzimidazole; D002417:Cattle; D014128:Chromomycin A3; D002865:Chromomycins; D004247:DNA; D003609:Dactinomycin; D008274:Magnesium; D009682:Magnetic Resonance Spectroscopy; D009690:Nucleic Acid Conformation; D013053:Spectrophotometry; D013950:Thymus Gland
D002865:Chromomycins; D003609:Dactinomycin; D004247:DNA; D014128:Chromomycin A3; D008274:Magnesium; D006690:Bisbenzimidazole