Watson-Crick base pairs duplex structures

Figure 2 Most common DNA/RNA binding modes. Left Strand invasion of homopyrimidine PNA into duplex DNA yields a PNA2-DNA triplex. Right Hybridization of mixed sequence PNA with complementary DNA or RNA produces Watson-Crick base-paired duplex structures.

Modulation of DNA structure and dynamics is also possible using base-pair mismatches. Mismatches exert little influence on the global structure of B-DNA duplexes. Locally, the extent of base stacking perturbation depends sensitively on the nature of the mismatch [139-141]. Therefore, while a CA mismatch introduces a significant distortion in local stacking, the well-stacked GA mismatch is, by many criteria, barely perceptible. The dynamics of mismatched base-pairs may also be significantly distinct from matched Watson-Crick base pairs [9]. We exploit these features of DNA mismatches to probe the sensitivity of DNA-mediated CT to base structure and dynamics. 

Fluorescence probes possessing the PyU base 46 selectively emit fluorescence only when the complementary base is adenine. In this case, the chromophore of is extruded to the outside of the duplex because of Watson-Crick base pair formation, and exposed to a highly polar aqueous phase. On the contrary, the duplex containing a PyU/N (N = G, C and T) mismatched base pair shows a structure in which the glycosyl bond of uridine is rotated to the syn conformation. In this conformation, the fluorophore is located at a hydrophobic site of the duplex. The control of base-specific fluorescence emission is based on the polarity change in the microenvironment where the fluorophore locates are dependent on the l>yU/A base-pair formation. 

For oxidation of G in duplex DNA, Steenken concluded that the proton on N-1 of G shifts spontaneously to N-3 of the cytosine in the normal Watson-Crick base pair to generate [C+(H)/G ]. Consistent with this proposal, calculations indicate that charge transfer in oxidized DNA is coupled with proton transfer from G to Experiments carried out in D2O also reveal a kinetic isotope effect for G oxidation, implicating a concerted proton-coupled electron transfer mechanism. However, density functional theory (DFT) calculations in the gas phase predict that the structure with a proton on G N-1 [C/HG ] is more stable than [C (H)/G ] by 1.4kcal/mol. " ... 

A critical structural issue with the subsequent incorporation of this type of chromophore-modified nucleosides into DNA duplexes is the assumption that it forms Watson-Crick base pairs with A as the counterbase. Our concern was that the large pyrene moiety may force the nucleosides into a syn conformation. 

The most striking structure that has been observed for a DNA duplex is the left-handed Z-form DNA having Watson-Crick base pairing and a zigzag sngar phosphate... 

Alexander Rich and his associates discovered a third type of DNA helix when they solved the structure of dCGCGCG. They found that this hexanucleotide forms a duplex of antiparallel strands held together by Watson-Crick base-pairing, as expected. What was surprising, however, was that this double helix was left-handed, in contrast with the right-handed screw sense of the A and B helices. Furthermore, the phosphates in the backbone zigzagged hence, they called this new form Z-DNA (Figure 27.10). 

The crystal structure of the duplex [r(guauaca)dC]2, which would be expected to form a self-complementary duplex with an AC mismatch, has been solved and instead shown to form only six Watson-Crick base pairs with two 3 -overhang-ing bases. There are two independent duplexes, each of which is bent, and which stack end to end to form a right-handed super-helix. The overhanging nucleotides are looped out of the structure, with the penultimate adenosine residues forming A-GC base triples. 

Synthetic peptide-nucleic acids (PNA, Scheme 14C) consisting of poly-N-(2-aminoethyl)glycine which is derivatized with nucleotides, are an interesting hybrid class of compounds, as they are found to form Watson-Crick base pairs with a complimentary peptide-nucleic acid, RNA, and DNA. The polypeptide backbone is achiral but chirality can be induced in the molecule or its assemblies in various ways. Tagging of the peptide-nucleic acid duplex with either L- or D-lysine leads to enantiomorphic structures with opposite CD spectra, analogous to the so-called sergeants-and-soldiers effect for polyisocyanates. When paired with RNA, the peptide-nucleic acid assumes the A-structure typical of RNA (see above). ... 

Glycol nucleic acid (GNA) is a simplified DNA analogue that has an acyclic three-carbon propylene glycol phosphodiester backbone (Fig. 4) (39). Variable temperature ultraviolet (UV) spectroscopy was used to demonstrate that complementary 18-mer GNA oligomers that contain T and A bases form antiparallel, helical duplexes based on Watson-Crick base pairing, which are more stable than the analogous DNA or RNA duplexes. No NMR or X-ray structure of GNA or hybrid GNA-DNA duplexes is yet available. Both GNA and LNA oligomers can be synthesized by standard solid-phase DNA synthetic methods, because the backbone of both molecules is formed by phosphodiester bonds. 

The Cu " "-containing, Q-modified GNA or PNA duplex adopted a structure similar to that of duplexes made exclusively from Watson-Crick base pairs, as indicated by CD spectroscopy (36, 112). In the case of Q-PNA, only the fully complementary duplexes showed a CD spectrum in the absence or in the presence of Cu " ", suggesting that structural differences due to the presence of... 

A crystal structure of the dimethylene sulfone-linked ribonucleotide (97) has been published. A mini-duplex containing two sets of Watson-Crick base pairs was observed which displayed many similar characteristics to that of a normal duplex containing RNA such as Cy-endo sugar pucker and anti conformation of the bases. 

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