DNA-drug interaction. The effects of vitamin C on the solution structure of Calf-thymus DNA studied by FTIR and laser Raman difference spectroscopy.
The interaction of calf-thymus DNA with L-ascorbic acid was investigated in aqueous solution at pH=7.6 with drug/DNA(P)(P=phosphate) molar ratios (r) of 1/40, 1/20, 1/10, 1/5, 1/2, 1 and 2. Fourier Transform infrared (FTIR) and laser Raman difference spectroscopic techniques were used to establish correlations between spectral modifications and drug binding mode, sequence specificity, DNA melting and conformational changes, as well as structural variations of drug-DNA complexes in aqueous solution. Infrared and Raman spectroscopic results showed that at low drug concentration (r = 1/40), a B to A-type conformational conversion occurs with minor drug-DNA interaction through A-T bases. At r=1/20, drug-PO2 binding was also observed with reduced intensity of DNA inplane vibrational frequencies, due to the increased base-stacking interaction and duplex stability. At r> 1/20, major perturbations of DNA bases were observed for both A-T and G-C base pairs in the major and minor grooves of the duplex. Evidence for this comes form the shift of the infrared and Raman vibrations of the A-T and G-C bases on drug interaction. At r>1/5, a minor helix destabilization occurred with participation of several DNA donor sites in drug complexation. The ascorbate anion interaction occurred mainly through H-bonding of the acid OH and C-O groups with DNA phosphate, bases and doxyribose donor atoms.
Neault
J F
JF
Centre de recherche en photobiophysique, Université du Québec à Trois-Rivières, Trois-Riviéres, Canada.
Naoui
M
M
Tajmir-Riahi
H A
HA
D000818:Animals; D001205:Ascorbic Acid / Q000737:chemistry*; D002417:Cattle; D004247:DNA / Q000737:chemistry*; D007834:Lasers; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman / Q000379:methods*; D013950:Thymus Gland / Q000737:chemistry*; D014732:Vibration
D012996:Solutions; D004247:DNA; D001205:Ascorbic Acid