X-ray crystal structure of A-form DNA 3a [5-OMe-DNA: 5′-G(^SedU)G(mo⁵dU)ACAC-3′] at 1.3 Å resolution (PDB ID: 3LTR). (A) Crystal images (bigger crystal: 0.2 × 0.2 × 0.3 mm). (B) Duplex structure; the yellow and red balls represent the selenium and oxygen atoms of the modified moieties, respectively. The 5-CH₃-O group points to the 5′-phosphate group, instead of the major groove. (C) Electron density map of mo⁵dU/dA base pair, with δ level = 1.0.

Hydration pattern comparison of the major grooves of ^SedU2-dG3-dU4. The superimposed local structures of the 5-OMe, 5-SMe and 5-SeMe DNAs are colored as red, blue and yellow, respectively. The H-bonds are shown in red for the 5-OMe DNA, and blue for the 5-S and 5-Se DNAs.

The calculated geometries of the 5-modifications in (A) N-Me-5-OMe-uracil; (B) N-Me-5-SMe-uracil and (C) N-Me-5-SeMe-uracil.

Chemical structures of uridine 1, 5-modified uridine derivatives (Xo⁵U, 2), 5-OMe, 5-SMe and 5-SeMe-uracil-containing oligonucleotides (3a, 3b and 3c) and 2′-SeMe-deoxyuridine (4, 2′-SeMe-dU or ^SedU).

Crystal structure comparisons. The red and yellow balls represent the oxygen and selenium atoms of the modified moieties, respectively. (A) The superimposed duplex structures of 5′-G(^SedU)G(mo⁵dU)ACAC-3′ (3a; in red; PDB ID: 3LTR; 1.30 Å resolution) and the corresponding native (in green; PDB ID: 1DNS; 2.0 Å resolution). (B) The superimposed single-strand structures of 3a (5-OMe-DNA; in red), 3b (5-SMe-DNA; in blue; PDB ID: 3IKI; 1.38 Å resolution), 3c (5-SeMe-DNA; in yellow; PDB ID: 3LTU; 1.40 Å resolution) and the corresponding native (in green; PDB ID: 1DNS). This high-resolution structure of 5-SeMe-DNA (3c), indicating no H-bond formation between the 5-SeMe and 5′-phosphate groups, updates the lower-resolution structure (PDB ID: 3BM0). (C) Superimposed modified dU4 and T4 residues in these four DNAs. (D) Superimposed local structures of dG3 in these four DNAs. (C and D are in the same color code as B). (E) The superimposed structures of mo⁵dU4/dA base pair of 3a (3LTR; in red), T4/dA of the native (1DNS; in green], and the native T4/dA base pair of 5′-G(^SedU)GTACAC-3′ (1Z7I; in cyan; 1.28 Å resolution). The native T4 of 5′-G(^SedU)GTACAC-3′ (PDB ID: 1Z7I; 1.28 Å resolution) is displayed, since the resolution of the native structure (1DNS; 2.0 Å resolution) is low and the highly ordered water molecules at T4 are not demonstrated. These two structures (1Z7I and 1DNS) are virtually identical.

Superimposed structures of the nucleotides. mo⁵dU4 of 3a [5′-G(^SedU)G(mo⁵dU)ACAC-3′; in red], ms⁵dU4 of 3b (blue), mSe⁵dU4 of 3c (yellow), and the native T4 of 5′-G(^SedU)GTACAC-3′ (PDB ID: 1Z7I; in cyan). The numbers in the corresponding colors as the lines represent the distances of these atoms in the same structure.