Triple-base pairs

Figure 6.5 Triple base pair for the Tetrahymena ribozyme (PDB 1X8W). Visualized using CambridgeSoft Chem3D Ultra 10.0 with notations in ChemDraw Ultra 10.0. (Printed with permission of CambridgeSoft Corporation.)...

Based on chemical considerations alone, ribozymes should be able to catalyze many different types of reactions. Ribozymes can maintain defined secondary and tertiary structures, just as protein enzymes do. Ribozymes can interact with substrates specifically via hydrogen bond networks, just as protein enzymes do. Finally, ribozymes have available to them a chemistry that, while more limited than of proteins, is substantial. RNA contains proton donors and acceptors with pK, values that cluster at 4 and 9.71 The critical lack of a good donor/acceptor with a pKt near 7 can be rectified by any of several simple expedients, such as modification of guanosine to 7-methylguanosine, protonation of triple base-paired cysto-sine,72 or inclusion of a proton donor/acceptor in an environment with a different polarity than water (in this respect, it is interesting to note that Dahm and Uhlenbeck have found that the cleavage reaction catalyzed by the hammerhead ribozyme is dependent on some dissociable proton with a pKa of 8.0).73... 

Triple-base pairs single-strand helix interactions)... 

Triple-base pairs occur when single-stranded nucleotides make hydrogen bonds with a Watson-Crick base pair. The third base may interact either within the major or the minor groove of the Watson-Crick base pair. For example, the folding of tRNA is stabilized by triple-base pairs between the junction loop and bases in the major groove of stem D. Also, a triple-base pair (UAU), between a U in a bulge and the U-A in the adjacent helix, is essential for the conformation of the binding site for human HIV protein Tat on TAR. 

Figure 5-7 Two base triplets that form in triple-stranded DNA and involve both Watson-Crick and Hoogsteen base pairing. (A) The triplet T A T, where the T (marked T ) of the third strand is hydrogen bonded as a Hoogsteen pair...

Fig. 41. Schematic representation of the columnar triple-helical superstructure derived from the X-ray data for (LP2, LU2) each spot represents a PU or UP base pair spots of the same type belong to the same supramolecular strand the dimensions are compatible with an arrangement of the PTP and UTU components along the strands indicated (see also text) the aliphatic chains stick out of the cylinder, more or less perpendicularly to its axis a single helical strand and the full triple helix are respectively represented at the bottom and at the top of the column [9.152].

Tn orcTer to extend these conformational energy studies to the analysis of multi-stranded nucleic acid systems, it is necessary to devise a procedure to identify the arrangements of the polynucleotide backbone that can acconmodate double, triple, and higher order helix formation. As a first step to this end, a computational scheme is offered here to identify the double helical structures compatible with given base pairing schemes. 

Since the IR spectrum of an RNA molecule has numerous features, IR spectroscopy is not limited to the determination of the fraction folded only. Depending upon the wavenumber of the transition, IR spectroscopy can distinguish A-U base pairs from G-C base pairs as well as the more complex base pairing schemes found in triple helices (Banyay et al., 2003 Brauns and Dyer, 2005). Similarly, base stacking interactions can be distinguished from base pairing interactions. It has even been shown that transfer RNAs of different species can be distinguished from their IR spectra (Thomas, 1969). 

The mechanism of retention on chiral phases that is based on multiple hydrogen bonding formation involves the formation of base pairs and triple hydrogen bonds between the solutes and the chiral stationary phase 95 Fundamental work in this area has been done by Hara and Dobashi,96 97 using amino acid amide and tartaric acid amide phases. In addition, N,N -2,6-pyridinediyl bis(alkanamides) chemically bonded to silica gel have been described for the resolution of barbiturates 95... 

Keiderling reported the VCD spectra of triple helices in ribonucleic acids by investigating the temperature dependent VCD features of a mixture of poly(rA) and poly(rU) [54]. The spectra of the triple helix are more complicated than those of a double strand, as expected. We have reported the VCD of a number of oligo deoxynu-cleotides with between four and twelve base pairs. These studies will be elaborated upon after a detailed discussion of the VCD features of polymeric DNA and RNA samples, for which the solution structures are well established. 

---