title: Structure of a DNA duplex containing a single 2'-O-methyl-beta-D-araT: combined use of NMR, restrained molecular dynamics, and full relaxation matrix refinement.
abstract: Two-dimensional 1H NMR spectroscopy was used to determine the solution structure of the double-stranded DNA oligonucleotide d(5'-CGCATATAGCC-3'): d(5'-GGCTAXATGCG-3'), where X is 1-(2-O-methyl-beta-D-arabinofuranosyl)thymine. The structure determination was based on a total relaxation matrix analysis of NOESY cross-peak intensities using the MARDIGRAS program. The improved RANDMARDI procedure was used during the calculations to include the experimental "noise" in the NOESY spectra. The NOE-derived distance restraints were applied in restrained molecular dynamics calculations. Twenty final structures each were generated for the modified DNA duplex from both A-form and B-form DNA starting structures. The root-mean-square deviation of the coordinates for the 40 structures was 0.82 A. The duplex adopts a normal B-DNA-type helix, and the spectra as well as the structure show that the modified nucleotide X adopts a C2'-endo (S) sugar conformation. There are no significant changes in the helix originating from the modified nucleotide. The CH3O group on X is directed toward the major groove, and there seems to be free space for further modifications at this position.
authors.affiliation: Department of Chemistry, Odense University, Denmark.
authors.forename: C H
authors.initials: CH
authors.lastname: Gotfredsen
authors.forename: H P
authors.initials: HP
authors.lastname: Spielmann
authors.forename: J
authors.initials: J
authors.lastname: Wengel
authors.forename: J P
authors.initials: JP
authors.lastname: Jacobsen
mesh_terms: D001087:Arabinonucleosides / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D012984:Software
chemical_list: C104446:1-(2'-O-methyl-arabinofuranosyl)thymine; D001087:Arabinonucleosides; D004247:DNA