INTERACTION OF DAUNOMYCIN WITH DEOXYDINUCLEOTIDE D-CPG BY 2-DIMENSIONAL PROTON MAGNETIC-RESONANCE TECHNIQUES

Interaction of daunomycin with d-CpG has been studied by taking 500-MH z 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 pro tons of d-CpG and the ring protons of drug chromophore shift upfield u p to similar to 0.27 ppm on interaction. Changes in chemical shift dec rease with temperature and are attributed to stacking of drug chromoph ore between CG and GC base pairs. The sugar is predominantly in the S conformational state for both cytosine and guanine residues in the rig ht-handed helix of the d-CpG complex. The glycosyl angles are about -1 20 +/- 20 degrees and -90 +/- 20 degrees for C and G residues, respect ively. In daunomycin, the spin-spin couplings-J(1'H-2'eqH), J(1'H-2'ax H), J(4'H-5'CH3), J(7H-8axH), and J(7H-8eqH)-are altered on complexati on 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 complexat ion. The observed intermolecular NOEs-CH6-2H, 1H; CH6, CH5-4OCH(3); CH 1'-2'axH; and GH4'-9COCH(3)-demonstrate the existence of specific conf ormation of the complex which reflects the anti-cancerous action of th e drug. (C) 1994 Academic Press,Inc.