NMR solution structures of [d(GCGAAT-3′-3′-αT-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 encompassed 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 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 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.