NMR solution structures of [d(GCGAAT-3 '-3 '-alpha T-5 '-5 '-CGC)(2)] and its unmodified control

We present the high-resolution solution structures of a self-complementary DNA decamer duplex featuring a single a-anomeric nucleotide per strand enco mpassed by a set of 3'-3' and 5'-5' phosphodiester linkages, d(GCG AAT-3'-3 '-alpha T-5'-5 '-CGC)(2), alphaT, and its unmodified control, d(GCGAATTCGC) (2), obtained by restrained molecular dynamics, Interproton distance and de oxyribose 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-) s tarting 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 s tem from the enhanced conformational exchange in the deoxyribose ring of th e cytidine following the 5'-5' linkage, the C3'-exo pseudorotation phase an gle of the a-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.