The solution structure of a DNA duplex containing a single 1-(2-O,3-C-ethylene-beta-D-arabinofuranosyl)thymidine nucleoside

The structure of a DNA duplex containing one 1-(2-O,3-C-ethylene-beta-D-ara binofuranosyl)-thymidine nucleoside (TS) modification was investigated by u se of two-dimensional H-1 NMR spectroscopy at 750 MHz. The structure of the d(CCGCT(5)AGCG):d(CGCTAGCGG) duplex (CT(5)AG) containing one of this 2'-O, 3'-C-linked bicycloarabino conformational restricted modification has been determined. We obtained inter-proton distance bounds from NOESY spectra by including a complete relaxation matrix analysis. These distance bounds were used as restraints in molecular dynamics (rMD) calculations. We also analy zed the fine structure of the cross peaks in a selective DQF-COSY spectra t o determine the sugar conformations of the nucleotides. Forty final structu res were generated for CT(5)AG from A-form and B-form dsDNA starting struct ures. The root-mean-square deviation (RMSD) of the coordinates for the fort y structures of the complex was 0.92 Angstrom. The structures were observed to be markedly irregular compared to canonical B-DNA, especially in terms of large variations in propeller twist anti buckle. Also, lack of stacking of two bases near the modification site is observed. The sugar conformation s of all the unmodified nucleotides are close to pure C2'-endo conformation . The structural feature of CT5AG was discussed in relation to the thermal stability and resistance towards exonucleolytic degradation.