title: High-throughput platform assay technology for the discovery of pre-microrna-selective small molecule probes.
abstract: MicroRNAs (miRNA) play critical roles in human development and disease. As such, the targeting of miRNAs is considered attractive as a novel therapeutic strategy. A major bottleneck toward this goal, however, has been the identification of small molecule probes that are specific for select RNAs and methods that will facilitate such discovery efforts. Using pre-microRNAs as proof-of-concept, herein we report a conceptually new and innovative approach for assaying RNA-small molecule interactions. Through this platform assay technology, which we term catalytic enzyme-linked click chemistry assay or cat-ELCCA, we have designed a method that can be implemented in high throughput, is virtually free of false readouts, and is general for all nucleic acids. Through cat-ELCCA, we envision the discovery of selective small molecule ligands for disease-relevant miRNAs to promote the field of RNA-targeted drug discovery and further our understanding of the role of miRNAs in cellular biology.
authors.affiliation: Program in Chemical Biology and ‡Department of Medicinal Chemistry, College of Pharmacy, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Lorenz
authors.forename: James M
authors.initials: JM
authors.lastname: Song
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Garner
mesh_terms: D055162:Biocatalysis; D055808:Drug Discovery / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods*; D035683:MicroRNAs / Q000378:metabolism*; D015335:Molecular Probes / Q000737:chemistry* / Q000378:metabolism*; D043244:Ribonuclease III / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D035683:MicroRNAs; D015335:Molecular Probes; D043244:Ribonuclease III