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Structure-Editing of Nucleic Acids for Selective Targeting of RNA

Kumar, Vaijayanti A and Ganesh, KN (2007) Structure-Editing of Nucleic Acids for Selective Targeting of RNA. In: Current Topics in Medicinal Chemistry, 17 (7). pp. 715-726.

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Abstract

The synthesis of backbone-modified nucleic acids has been an area of very intense research over the last two decades. The main reason for this research activity is the instability of nucleic acid based drugs in the intracellular conditions. Changes in the sugar-phosphate backbone invariably bring about the changes in the complementation properties of the nucleic acids. The naturally occurring deoxyribose- (DNA) and ribose (RNA)sugar-phosphate backbones are endowed with considerable differences in their binding affinities towards themselves. This occurs because of the different sugar conformations prevalent in DNA and RNA and the subtle structural changes accruing from these in hydrogen bonding, base-stacking interactions and hydration of major/minor grooves. The six-atom phosphodiester linkages and pentose-sugars give immense opportunities for chemical modifications that lead o several backbone-modified nucleic acid structures. This aticle is focused on such modifications that impart RNA-selective binding properties to the modified nucleic acid mimics and the rationale behind the said selectivity. It is ound that the six-atom sugar-phosphate backbone could be eplaced by either one-atom extended or one-atom edited epeating units, leading to the folded or extended eometries to maintain the internucleoside distance-complementarity. ther important contributions come from electronegativity of he substituent groups, hydration in the major/minor groove, ase stacking etc.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to Bentham Science Publishers Ltd.
Department/Centre: Division of Physical & Mathematical Sciences > Physics
Date Deposited: 06 Jun 2008
Last Modified: 27 Aug 2008 13:26
URI: http://eprints.iisc.ernet.in/id/eprint/14213

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