Derivatives of Nucleic Acids for Selective RNA Targeting
Pp. 386-411 (26)
Vaijayanti A. Kumar
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 being the instability of nucleic acid based drugs in the intracellular
conditions. The 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 groves. The sixatom
phosphodiester linkages and pentose-sugars give immense opportunities for
chemical modifications that lead to several backbone-modified nucleic acid
structures. This article 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 found that the six-atom sugar-phosphate backbone could be
replaced by either one-atom extended or one-atom edited repeating units, leading
to the folded or extended geometries to maintain the internucleoside distancecomplementarity.
Other important contributions come from electronegativity of the
substituent groups, hydration in the major/minor grove, base stacking etc.
RNA targeting, antisense, modified oligonucleotides.
Organic Chemistry Division, National Chemical Laboratory, Pune, 411008 India