Watson-Crick pairing base pair stability

Sarai, A., and M. Saito. 1985. Theoretical Studies on the Interaction of Proteins with Base Paris. II. Effect of External H-Bond Interactions on the Stability of Guanine-Cytosine and Non-Watson-Crick Pairs. Int. J. Quantum Chem. 28, 399-409. 

Fig. 20.8. Three-dimensional structure of phenylalanine specific tRNA from yeast. Watson-Crick type base pairs indicated by slabs, nonstandard base-base interactions that stabilize the tertiary structure are denoted a to h. Invariant and semi-invariant nucleotides are shaded, the four double helical regions are indicated by a a-(amino add) arm, Tarm, D arm, a.c. (anticodon arm [696]...

One problem for targeting RNA is that the A U and G U base pairs have similar stability, and G U wobble pairs account for almost half of known non-Watson-Crick pairs. 2-Thiouridine will increase the specificity for pairing with adenosine by a factor of 10. It has been reported that the complete substitution of pyrimidines by C5-propynyl pyrimidines enhances this specificity 100-fold without altering base pairing specificity. " ... 

In three dimensions, tRNAs fold into an L-shaped structure in which the acceptor stem and T C arm coaxially stack to form one part of the L known as the minihelix, and the D and anticodon arms likewise stack to form the other part of the molecule. This structure is facilitated and stabilized by tertiary interactions at the corner of the L that bring together the D and variable loops. The nucleotides involved in these interactions are typically invariant or semi-invariant, indicating that the tRNA L shape is universal. While most base pairs in tRNA helices are canonical Watson-Crick pairs, the tertiary interactions at the corner of the L make use of some unusual hydrogen-bonding conformations. For example, nearly all tRNAs contain a U8 A14 reverse Hoogsteen base pair, and several base triples (where three bases are paired together) are also typically present at the core of the structure. 

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