Читать книгу Chemistry and Biology of Non-canonical Nucleic Acids - Naoki Sugimoto - Страница 22

Mismatched base pairs between purine and pyrimidine nucleobases are known as transition mismatches. G·T and G·U mismatches can form two hydrogen bonds, which are usually known as typical “wobble” base pairs, by shifting the nucleobase geometry from that of Watson–Crick base pairs (Figure 2.2). These mismatches are one of the most stable mismatches in DNA and RNA duplexes (Tables 2.1 and 2.2). G·U base pair is frequently observed in natural RNAs. It is because that both guanine and uracil take anti conformation in their glycosidic bond angles that are the same with Watson–Crick base pairs and the distance and geometric arrangement of C1′ atoms of the sugars do not largely change compared with the canonical duplex. Thus, there is no significant worsening of base stacking and littler perturbation of the duplex conformation. Adenine and cytosine also form two hydrogen bonds as similar way as the G·T(U) mismatch when the adenine nucleobase is protonated (Figure 2.2). Formation of the A⁺·C mismatched base pair is demonstrated by X-ray diffraction analysis using dodecamer oligonucleotide strand [7]. However, neutral A·C mismatches are in equilibrium between the wobble and reverse wobble forms, each of which only forms one hydrogen bond. Thus, A·C mismatch is much less stable than G·T(U) mismatch in a physiological condition (Tables 2.1 and 2.2).

Figure 2.2 Wobble base pairs in duplexes. Chemical structures of G-T (a), G-U (b), and A⁺-C (c) wobble base pairs. N1 atom of adenine nucleobase is protonated. (d) Structure of B-form DNA duplex containing G-T wobble base pairs (PDB ID: 113D). (e) Structure of A-form RNA duplex containing two consecutive G-U wobble base pairs (PDB ID: 433D). (f) Structure of B-form DNA duplex containing A⁺-C wobble base pairs (PDB ID: 1D99). Nucleobases forming the wobble base pairs are emphasized dark. Hydrogen bonds in the wobble base pairs are shown in dashed lines.