Lb. Jorgensen et al., The solution structure of a DNA duplex containing a single 1-(2-O,3-C-ethylene-beta-D-arabinofuranosyl)thymidine nucleoside, J BIO STRUC, 18(1), 2000, pp. 45-57
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.