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The chemical nature of the 2'-substituent in the pentose-sugar dictates the pseudoaromatic character of the nucleobase (pKa) in DNA/RNA
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Bioorganic Chemistry.
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2006 (English)In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 4, no 9, 1675-1686 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2006. Vol. 4, no 9, 1675-1686 p.
National Category
Organic Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-96276DOI: 10.1039/B601460GOAI: oai:DiVA.org:uu-96276DiVA: diva2:170795
Available from: 2007-10-16 Created: 2007-10-16 Last updated: 2015-05-19Bibliographically approved
In thesis
1. Structural and Biophysical Studies of Nucleic Acids
Open this publication in new window or tab >>Structural and Biophysical Studies of Nucleic Acids
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis is based on six research publications concerned with (i) study of the molecular structures and dynamics of modified nucleosides; (ii) investigation of the effect of incorporation of modified nucleosides on the structure of DNA; (iii) examination of the effect of the sugar modifications on the pseudo-aromatic properties (pKa) of the nucleobases; (iv) analysis of the effect of the CH-π interactions on the relative stability of the DNA-RNA hybrid duplexes. The structural stability of the nucleic acids as well as their behavior in molecular recognition is dominated by hydrogen bonding and stacking interactions beside other non-covalent interactions. Naturally occurring nucleosides are found to have some specific functions. Modifications of nucleic acids, followed by studies of the resulting structural, chemical and functional changes, contribute to an understanding of their role in various biochemical processes, such as catalysis or gene silencing. In papers I-III, analysis of the structures of modified thymidine nucleosides with 1′,2′-(oxetane or azetidine) and 2′,4′-(LNA, 2′-amino LNA, ENA, and Aza-ENA) conformationally constrained sugar moieties, and dynamics of the modified nucleosides by NMR, ab initio, and molecular dynamics simulations are discussed. Based on whether the modification leads to 1′,2′- or 2′,4′- constrained sugar moieties, it is found that they fall into two distinct categories characterized by their respective internal dynamics of the glycosidic and backbone torsions as well as by their characteristic NE-type (P = 37° ± 27°, Φm = 25° ± 18°) for 1′,2′-constrained nucleosides, and N-type (P = 19° ± 8°, Φm = 48° ± 4°) for 2′,4′-constrained systems, respectively. Moreover, each group has different conformational hyperspace accessible. The effect of the incorporation of 1′,2′-oxetane locked thymidine nucleoside on the structure and dynamics of the Dickerson-Drew dodecamer, d(CGCGAATTCGCG)2, determined by NMR, is discussed in the paper IV. It shows that the incorporation of oxetane locked T into the dodecamer has made local structural deformations and perturbation in base pairing, where the modification is included. The modulations of physico-chemical properties of the nucleobases in nucleotides by the C2′-modification of the sugar (paper V), 5′-phosphate group, and the effect of constrained pentofuranosyl moiety (sugar, paper III) have been studied. CH-π interactions between the methyl group of thymidine and the neighboring aromatic nucleobase are shown to increase the relative stability of the DNA-RNA hybrid duplexes over the isosequential RNA-DNA duplexes or vice versa (paper VI).

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 60 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 349
Keyword
Organic chemistry, nucleic acids, Nuclear Magnetic Resonance, molecular dynamics, sugar modified nucleosides, pKa, Organisk kemi
Identifiers
urn:nbn:se:uu:diva-8245 (URN)978-91-554-6982-5 (ISBN)
Public defence
2007-11-06, 113a, B7, Husargatan 3, Uppsala, 09:30
Opponent
Supervisors
Available from: 2007-10-16 Created: 2007-10-16Bibliographically approved

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Plashkevych, Oleksandr

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