<p>This thesis is based on ten publications (Papers I-X). The phosphodiester backbone makes DNA or RNA to behave as polyelectrolyte, the pentose sugar gives the flexibility, and the aglycones promote the self-assembly or the ligand-binding process. The hydrogen bonding, stacking, stereoelectronics and hydration are few of the important non-covalent forces dictating the self-assembly of DNA/RNA. The pH-dependent thermodynamics clearly show (Papers I and II) that a change of the electronic character of aglycone modulates the conformation of the sugar moiety by the tunable interplay of stereoelectronic anomeric and <i>gauche</i> effects, which are further transmitted to steer the sugar-phosphate backbone conformation in a cooperative manner. 3'<i>-</i>anthraniloyl<b> </b>adenosine<b> </b>(a mimic of 3'-teminal CC<u>A</u><sub>OH</sub> of the aminoacyl-tRNA<sup>Phe</sup>) binds to EF-Tu*GTP in preference over 2'<i>-</i>anthraniloyl<b> </b>adenosine<b>, </b>thereby showing (Paper III) that the 2’-<i>endo</i> sugar conformation is a more suitable mimic of the transition state geometry than the 3’<i>-endo</i> conformation in discriminating between correctly and incorrectly charged aminoacyl-tRNA<sup>Phe</sup> by EF-Tu during protein synthesis. The presence of 2'-OH in RNA distinguishes<sup> </sup>it from DNA both functionally<sup> </sup>as well as structurally. This work (Paper IV) provides straightforward NMR evidence to show that the 2'-OH is intramolecularly hydrogen bonded with the vicinal 3'-oxygen, and the exposure of the 3'<i>-</i>phosphate of the ribonucleotides to the bulk water determines the availability of the bound water around the vicinal 2'-OH, which then can play various functional role through inter- or intramolecular interactions. The pH-dependent <sup>1</sup>H NMR study with nicotinamide derivatives demonstrates (Paper V) that the cascade of intramolecular cation (pyridinium)-π(phenyl)-CH(methyl) interaction in edge-to-face geometry is responsible for perturbing the p<i>K</i><sub>a</sub> of the pyridine-nitrogen as well as for the modulation of the aromatic character of the neighboring phenyl moiety, which is also supported by the T<sub>1</sub> relaxation studies and <i>ab initio</i> calculations. It has been found (Papers VI-IX) that the variable intramolecular electrostatic interaction between electronically coupled nearest neighbor nucleobases (steered by their respective microenvironments) can modulate their respective pseudoaromatic characters. The net result of this pseudoaromatic cross-modulation is the creation of a unique set of aglycones in an oligo or polynucleotide, whose physico-chemical properties are completely dependent upon the propensity and geometry of the nearest neighbor interactions (extended genetic code). The propagation of the interplay of these electrostatic interactions across the hexameric ssDNA chain is considerably less favoured (effectively up to the fourth nucleobase) compared to that of the isosequential ssRNA (up to the sixth nucleobase). The dissection of the relative strength of basepairing and stacking in a duplex shows that stability of DNA-DNA duplex weakens over the corresponding RNA-RNA duplexes with the increasing content of A-T/U base pairs, while the strength of stacking of A-T rich DNA-DNA duplex increases in comparison with A-U rich sequence in RNA-RNA duplexes (Paper X).</p>
| Identifer | oai:union.ndltd.org:UPSALLA/oai:DiVA.org:uu-3825 |
| Date | January 2003 |
| Creators | Acharya, Parag |
| Publisher | Uppsala University, Department of Bioorganic Chemistry, Uppsala : Acta Universitatis Upsaliensis |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, text |
| Relation | Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, 1104-232X ; 914 |
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