title: NMR solution structure of dsDNA containing a bicyclic D-arabino-configured nucleotide fixed in an O4'-endo sugar conformation.
abstract: [3.2.0]bcANA is a D-arabino-configured bicyclic nucleotide with a 2'-O,3'-C-methylene bridge. We here present the high-resolution NMR structure of a [3.2.0]bcANA modified dsDNA nonamer with one modified nucleotide incorporated. NOE restraints were obtained by analysis of NOESY cross peak intensities using a full relaxation matrix approach, and subsequently these restraints were incorporated into a simulated annealing scheme for the structure determination. In addition, the furanose ring puckers of the deoxyribose moieties were determined by analysis of COSY cross peaks. The modified duplex adopts a B-like geometry with Watson-Crick base pairing in all base pairs and all glycosidic angles in the anti range. The stacking arrangement of the nucleobases appears to be unperturbed relative to the normal B-like arrangement. The 2'-O,3'-C-methylene bridge of the modified nucleotide is located at the brim of the major groove where it fits well into the B-type duplex framework. The sugar pucker of the [3.2.0]bcANA nucleotide is O4'-endo and this sugar conformation causes a change in the delta backbone angle relative to the C2'-endo deoxyribose sugar pucker. This change is absorbed locally by slight changes in the epsilon and zeta angles of the modified nucleotide. Overall, the [3.2.0]bcANA modifications fits very well into a B-like duplex framework and only small and local perturbations are observed relative to the unmodified dsDNA of identical base sequence.
authors.affiliation: Department of Chemistry, University of Southern Denmark, DK-5230 Odense M, Denmark.
authors.forename: Henning V
authors.initials: HV
authors.lastname: Tømmerholt
authors.forename: Nanna K
authors.initials: NK
authors.lastname: Christensen
authors.forename: Poul
authors.initials: P
authors.lastname: Nielsen
authors.forename: Jesper
authors.initials: J
authors.lastname: Wengel
authors.forename: Paul C
authors.initials: PC
authors.lastname: Stein
authors.forename: Jens Peter
authors.initials: JP
authors.lastname: Jacobsen
authors.forename: Michael
authors.initials: M
authors.lastname: Petersen
mesh_terms: D001089:Arabinose / Q000031:analogs & derivatives*; D001483:Base Sequence; D002236:Carbohydrate Conformation; D004247:DNA / Q000737:chemistry*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry
chemical_list: D009841:Oligonucleotides; D012996:Solutions; D004247:DNA; D001089:Arabinose