Several biophysical techniques such as fluorescence, NMR, X-ray crystallography, to name a few, have been very useful in studying nucleic acids.1 However, the current knowledge on the structure-function relationship of nucleic acids, especially RNA, is limited and hence, it is essential to develop robust tools to understand how nucleic acid structure complements its function. Towards this endeavour, we have developed a new �double-duty� nucleobase analog, based on a (selenophen-2-yl)pyrimidine core, which serves as a fluorescence probe to study the function of nucleic acids in real time and as an anomalous scattering label (selenium atom) for the phase determination in X-ray crystallography (Figure 1).2 The selenophene-modified nucleoside can be effectively incorporated into DNA and RNA oligonucleotides by enzymatic as well as by solid-phase synthesis protocol. The nucleoside is minimally perturbing within oligonucleotides and exhibits probe like properties such as sensitivity to microenvironment and conformation changes. Utilizing these properties, we have site-specifically incorporated the nucleoside analog into therapeutically relevant nucleic acid motifs (e.g., bacterial ribosomal decoding site RNA and telomeric DNA repeats), and have studied their conformational changes during folding and recognition processes. In this presentation, the design, synthesis, photophysical characterization and applications of the selenophene-modified nucleoside analog will be described.   References:1. Sinkeldam, R. W.; Greco, N. J.; Tor, Y. Chem. Rev. 2010 , 110, 2579.2. Pawar, M. G.; Nuthanakanti, A.; Srivatsan, S. G. Bioconjugate Chem. 2013 , 24, 1367.

Heavy atom containing fluorescent nucleoside analog probe for the fluorescence detection of nucleic acid-ligand binding and X-ray crystallography

248th National Meeting (2014)

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