<p>This thesis is based on six papers, Papers I-VI, focusing on the interplay between the stabilizing elements of nucleic acids self-assembly; hydrogen bonding, stacking and solvent effects. In Paper I we investigate how the substitution of the O4' for CH<sub>2</sub> in the sugar moiety of adenosine (2'-deoxyaristeromycin) at the A<sup>6</sup> position of the Dickerson-Drew dodecamer makes the two modified bases exist in a dynamic equilibrium between Hoogsteen and Watson-Crick base pairing in the NMR time scale. Paper II is a structural study of the incorporation of 1-(1',3'-<i>O</i>-anhydro-<i>β</i>-D-psicofuranosyl)thymine in the T<sup>7</sup> position of the Dickerson-Drew dodecamer. NMR constrained molecular dynamics and hydration studies show the base-base distortions caused by the introduction of a North-type locked sugar in an otherwise B-type DNA•DNA duplex. Paper III shows that the stacking distortion caused by the 1-(1',3'-<i>O</i>-anhydro-<i>β</i>-D-psicofuranosyl)thymine building block perturbs the charge transfer similar to a DNA mismatch. Paper IV highlights how the sequence context affects the physico-chemical properties, monitored by the p<i>K</i><i>a</i> of guanine itself as well as how the charge perturbation is experienced by the neighboring bases, in ssDNA and ssRNA. Paper V focuses on the differences between the structural equilibria of single-stranded ssDNA and ssRNA. Directional differences in single-stranded stacking between ssDNA and ssRNA are identified and provide a basis to explain directional differences in p<i>K</i><i>a</i> modulation and dangling-end stabilization. In Paper VI the thermodynamic gains of dangling ends on DNA and RNA core duplexes are found to correlate with the X-ray geometries of dangling nucleobases relative to the hydrogen bonds of the closing base pairs.</p>
| Identifer | oai:union.ndltd.org:UPSALLA/oai:DiVA.org:uu-5867 |
| Date | January 2005 |
| Creators | Isaksson, Johan |
| Publisher | Uppsala University, Department of Bioorganic Chemistry, Uppsala : Institutionen för bioorganisk kemi |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, text |
| Relation | Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, 1651-6214 ; 71 |
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