Aramini J M, Mujeeb A, Germann M W
Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Nucleic Acids Res. 1998 Dec 15;26(24):5644-54. doi: 10.1093/nar/26.24.5644.
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.
我们展示了一种自互补DNA十聚体双链体的高分辨率溶液结构，其每条链具有单个α-异头核苷酸，被一组3'-3'和5'-5'磷酸二酯键所包围，即d(GCGAAT-3'-3'-αT-5'-5'-CGC)2、αT及其未修饰的对照d(GCGAATTCGC)2，这些结构是通过受限分子动力学获得的。质子间距离和脱氧核糖环扭转角约束分别从同核NOESY和DQF-COSY数据推导得出。对于对照双链体和αT双链体，从两个不同的（A-和B-）起始模型都观察到了良好的全局收敛。这两种双链体的最终平均结构高度同源，总体上具有右手B-DNA双链体的特征。然而，这两种结构之间的局部差异源于5'-5'键连接后胞苷脱氧核糖环中增强的构象交换、α-核苷酸的C3'-外假旋转相角以及3'-3'和5'-5'磷酸二酯键中不寻常的主链扭转。本文报道的结构数据与由这些修饰组成的反义治疗剂的设计相关。
