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 approximately 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 degrees and -90 +/- 20 degrees 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.
Barthwal
R
R
Department of Biosciences and Biotechnology, University of Roorkee, India.
Mujeeb
A
A
Govil
G
G
D004247:DNA / Q000737:chemistry*; D003630:Daunorubicin / Q000737:chemistry*; D003845:Deoxycytosine Nucleotides / Q000737:chemistry*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008968:Molecular Conformation; D009690:Nucleic Acid Conformation; D013816:Thermodynamics
D003845:Deoxycytosine Nucleotides; C037781:deoxycytidylyl-(3'-5')-deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine; D003630:Daunorubicin