Discovery of RNA binding small molecules using small molecule microarrays

Abstract

New methods to identify RNA-binding small molecules open yet unexplored opportunities for the pharmacological modulation of RNA-driven biology and disease states. One such approach is the use of small molecule microarrays (SMMs). Typically,SMMs are generated by spatially arraying and covalently linking a library of small molecules to a glass surface. Next,incubation of the arrays with a fluorescently labeled RNA reveals binding interactions that are detected upon slide imaging. The relative ease with which SMMs are manufactured enables the screening of multiple oligonucleotides in parallel against tens of thousands of small molecules,providing information about both binding and selectivity of identified RNA-small molecule interactions. This approach is useful for screening a broad variety of structurally and functionally diverse RNAs. Here,we present a general method for the preparation and use of SMMs to rapidly identify small molecules that selectively bind to an RNA of interest.