Structural and biological evaluation of Xylonucleic acids (XNA) as a potential tool for synthetic biology/oligonucleotide based therapeutic application.

Xylonucleic acid (XNA) is 3-diastereomeric epimer of RNA. From the structural point of view this is a minimal chemical modification/alteration in the sugar phosphate backbone of RNA (still containing furanose sugars). Recently we have studied the 2-deoxy congener (Xylose-DNA or dXNA) of Xylonucleic acid and identified favorable structural and biological properties for potential synthetic biology application (Maiti et. al., Chem. Eur. J., 2012, 18, 869). In view of the potential use of Xylose based nucleic acids in synthetic biology or in RNA targeting therapeutics, we propose to study in detail the structural, biochemical and biological properties of Xylonucleic acid (XNA). So far, XNA oligonucleotides have not been synthesized and little is known about their structural and biological properties. In this post-doctoral project, several Xylo-oligonucleotides will be synthesized to study their conformational/structural properties, thermodynamic stability, and pairing properties with itself and with the complementary DNA/RNA by using several biophysical techniques (UV/CD/NMR spectroscopy). Based on the results of these preliminary biophysical studies they will be selected for a suitable biological application. Further detailed biochemical and biological/therapeutic evaluation will be performed partly in collaboration with other laboratories.

Keywords:XNA, Nucleic acids, Diastereomeric, Epimer, RNA