Sugars conformation

The significance of n.m.r. spectroscopy for structural elucidation of carbohydrates can scarcely be underestimated, and the field has become vast with ramifications of specialized techniques. Although chemical shifts and spin couplings of individual nuclei constitute the primary data for most n.m.r.-spectral analyses, other n.m.r. parameters may provide important additional data. P. Dais and A. S. Perlin (Montreal) here discuss the measurement of proton spin-lattice relaxation rates. The authors present the basic theory concerning spin-lattice relaxation, explain how reliable data may be determined, and demonstrate how these rates can be correlated with stereospecific dependencies, especially regarding the estimation of interproton distances and the implications of these values in the interpretation of sugar conformations. 

We will start by presenting new advances from the NMR methodological viewpoint to later describe some key examples of applications of NMR for sugar conformation determination, by discriminating between the free and bound state and also from natural and synthetic sugars (or mimetics thereof). 

In nucleic acids, the cross-correlation studies were applied to investigation of the sugar conformation [101-103] of the phosphodiester backbone [65] as well as to some more spe-... 

By combining the quantitative approach [23] to extract cross-correlated relaxation with resolution enhancement methods using restricted coherence transfer in a so-called forward directed TOCSY [27], Richter et al. could determine the ribose sugar conformation for all but two residues in a uniformly 13C,15N labeled 25mer RNA [28] and compare them to 3J(H, H) values determined using a forward-directed HCC-TOCSY-CCH-E.COSY experiment [29]. 

The trCCR experiment has been apphed to study the boimd conformation of a nucleotide analog bound to Elongation Factor Tu [8,23]. Measurements of the CCR-rates /hi ci C2 H2 and /h3 c3 C4 H4 of the C-labelled nucleotide in the presence of its receptor, resulted in an unambiguous determination of the sugar conformation of the nucleotide. 

Asano N, Kizu H, Oseki K, Tomioka E, Matsui K, Okamoto M, Baba M. (1995) A-Alkylated nitrogen-in-the-ring sugars Conformational basis of inhibition of glycosidases and HIV-1 rephcation. JMed Chem 38 2349-2356. 

Figure l i The structure of the CpG-acrldine orange intercalator complex. The C2 endo sugar conformation at the 3 end of the BNA chain surrounding the intercalator is indicated. 

This is essentially the same structure published by Crick and Watson (24) and supports their general proposal for the structure of DNA. Although they intended to model B-DNA, once they had assigned the wrong sugar conformation, the other conformationl peculiarities followed. 

Are products with different sugar conformations and/or base orientations (isomers) formed ... 

Fig. 17.4. Description of the main sugar conformations in nucleosides, nucleotides, and nucleic acids [522]...

Another feature associated with B-DNA, but not with A- and Z-DNA, is the extra water molecule located between free phosphate oxygen and thymine methyl groups. Apparently, this water molecule is loosely bound and disappears upon dehydration, allowing the sugar conformation to change from C(2>endo to C(3 )-endo. 

There are two reports describing the use of nucleosides with other sugar conformations. A method for preparing internally P-labelled l-DNA has been described using T4 polynucleotide kinase. Chimeric DNA composed of tandem a- and p-anomeric strands have been used in TFOs and shown to have enhanced thermal stability compared to all a- or p-anomeric oligonucleotides. ... 

In addition to using /-scalar coupling data (see above), several other methods have been proposed to estimating sugar conformations in RNA based on the 13C-4H dipole-dipole cross-correlated relaxation,289 based on the cross-correlated relaxation rates involving 13C CSA and 13C-4H dipolar interactions,290 and based on the 13C chemical shifts of sugar carbons.291... 

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