Identification of Nucleic Acid Binding Small Molecules

Division Of Basic Sciences - Nci

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Abstract

In this project, we use small molecule microarrays to identify RNA- and DNA- binding small molecules. We have assembled a library of 65,000 small molecules that may be screened in the microarray format. In each case, molecules are printed on to glass slides using a microarrayer robot and covalently linked to the surface. Next, fluorescently labeled oligonucleotides with defined structures (such as hairpins or quadruplexes) are incubated on array surfaces. Spots that increase in fluorescence intensity are scored as binding. Once hit molecules of interest are identified from the screen, they are characterized through chemical synthesis, biochemical and biophysical analyses, and if possible in cellular assays to confirm biological activity as well as binding to the oligonucleotide. In this project, we place an interest in RNA and DNA structures involved in regulating gene expression.