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SCAN ^TM—A High-Throughput Assay for Detecting Small Molecule Binding to RNA Targets

Department of Biology, Anadys Pharmaceuticals, Inc., San Diego, California

Shaohui Wang

Department of Biology, Anadys Pharmaceuticals, Inc., San Diego, California

Bin Li

Department of Biology, Anadys Pharmaceuticals, Inc., San Diego, California

James R. Appleman

Department of Biology, Anadys Pharmaceuticals, Inc., San Diego, California

Peggy A. Thompson

Department of Biology, Anadys Pharmaceuticals, Inc., San Diego, California, pthompson{at}anadyspharma.com

A novel optical-based high-throughput screening technology has been developed for increasing the rate of discovering chemical leads against RNA targets. SCAN^TM ( Screen for Compounds with Affinity for Nucleic Acids) is an affinity-based assay that identifies small molecules that bind and recognize structured RNA elements. This technology provides the opportunity to conduct high-throughput screening of a new class of targets—RNA. SCAN^TM offers many attractive features including a simple homogeneous format, low screening costs, and the ability to use common laboratory equipment. A SCAN^TM assay was developed for the HCV IRES Loop IIId RNA domain. A high-throughput screen of our entire compound library resulted in the identification of small molecule ligands that bind to Loop IIId. The Z' values were greater than 0.8, showing this to be a robust high-throughput screening assay. A correlation between SCAN^TM EC₅₀ and K_D values is reported suggesting the ability to use the assay for compound optimization. (Journal of Biomolecular Screening 2009:219-229)

Key Words: SCAN^TM • HCV IRES Loop IIId • RNA • high-throughput screening • affinity-based FRET assay

This version was published on March 1, 2009

Journal of Biomolecular Screening, Vol. 14, No. 3, 219-229 (2009)
DOI: 10.1177/1087057108330111


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