Interaction of Daunomycin with Deoxydinucleotide d-CpG by Two-Dimensional Proton Magnetic Resonance Techniques

Interaction of daunomycin with d-CpG has been studied by taking 500-MHz proton NMR spectra of a mixture of 5.5 mM daunomycin with 11.0 mM d-CpG in the temperature range 277-320 K. The 2D COSY and NOESY spectra of the complex are investigated at 297 K. The nonexchangeable base protons of d-CpG and the ring protons of drug chromophore shift upfield up to ∼0.27 ppm on interaction. Changes in chemical shift decrease with temperature and are attributed to stacking of drug chromophore between CG and GC base pairs. The sugar is predominantly in the S conformational state for both cytosine and guanine residues in the right-handed helix of the d-CpG complex. The glycosyl angles are about −120 ± 20° and −90 ± 20° for C and G residues, respectively. In daunomycin, the spin-spin couplings-J(1′H-2′eqH), J(1′H-2′axH), J(4′H-5′CH3), J(7H-8axH), and J(7H-8eqH)-are altered on complexation with d-CpG. Further, the interproton distances-1′H-2′axH, 7H-8axH, 7H-8eqH, 5′H-8axH, and 5′H-8eqH-are altered significantly on complexation. The observed intermolecular NOEs-CH6-2H, 1H; CH6, CH5-4OCH3; CH1′-2′axH; and GH4′-9COCH3-demonstrate the existence of specific conformation of the complex which reflects the anti-cancerous action of the drug.