title: NMR solution structures of [d(GCGAAT-3'-3'-alphaT-5'-5'-CGC)2] and its unmodified control.
abstract: We present the high-resolution solution structures of a self-complementary DNA decamer duplex featuring a single alpha-anomeric nucleotide per strand encompassed by a set of 3'-3' and 5'-5' phosphodiester linkages, d(GCGAAT-3'-3'-alphaT-5'-5'-CGC)2, alphaT, and its unmodified control, d(GCGAATTCGC)2, obtained by restrained molecular dynamics. Interproton distance and deoxyribose ring torsion angle restraints were deduced from homonuclear NOESY and DQF-COSY data, respectively. For both the control and alphaT duplexes, excellent global convergence was observed from two different (A- and B-) starting models. The final average structures of the two duplexes are highly homologous, and overall possess the traits characteristic of right-handed B-DNA duplexes. However, localized differences between the two structures stem from the enhanced conformational exchange in the deoxyribose ring of the cytidine following the 5'-5' linkage, the C3'- exo pseudorotation phase angle of the alpha-nucleotide, and unusual backbone torsions in the 3'-3' and 5'-5' phosphodiester linkages. The structural data reported here are relevant to the design of antisense therapeutics comprised of these modifications.
authors.affiliation: Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Aramini
authors.forename: A
authors.initials: A
authors.lastname: Mujeeb
authors.forename: M W
authors.initials: MW
authors.lastname: Germann
mesh_terms: D015342:DNA Probes / Q000737:chemistry*; D018076:DNA, Complementary; D009682:Magnetic Resonance Spectroscopy; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry*
chemical_list: D015342:DNA Probes; D018076:DNA, Complementary; D009841:Oligonucleotides