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Biology 2014, 3(2), 281-294; doi:10.3390/biology3020281

Screening for Antifibrotic Compounds Using High Throughput System Based on Fluorescence Polarization

College of Medicine, Florida State University, 1115 W. Call St., Tallahassee, FL 32306, USA
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Received: 15 January 2014 / Revised: 28 February 2014 / Accepted: 1 April 2014 / Published: 10 April 2014
(This article belongs to the Special Issue Screening for Biologically Active Compounds)
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Abstract

Fibroproliferative diseases are one of the leading causes of death worldwide. They are characterized by reactive fibrosis caused by uncontrolled synthesis of type I collagen. There is no cure for fibrosis and development of therapeutics that can inhibit collagen synthesis is urgently needed. Collagen α1(I) mRNA and α2(I) mRNA encode for type I collagen and they have a unique 5' stem-loop structure in their 5' untranslated regions (5'SL). Collagen 5'SL binds protein LARP6 with high affinity and specificity. The interaction between LARP6 and the 5'SL is critical for biosynthesis of type I collagen and development of fibrosis in vivo. Therefore, this interaction represents is an ideal target to develop antifibrotic drugs. A high throughput system to screen for chemical compounds that can dissociate LARP6 from 5'SL has been developed. It is based on fluorescence polarization and can be adapted to screen for inhibitors of other protein-RNA interactions. Screening of 50,000 chemical compounds yielded a lead compound that can inhibit type I collagen synthesis at nanomolar concentrations. The development, characteristics, and critical appraisal of this assay are presented. View Full-Text
Keywords: fibrosis; antifibrotic drugs; RNA binding protein; fluorescence polarization fibrosis; antifibrotic drugs; RNA binding protein; fluorescence polarization
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Stefanovic, B.; Stefanovic, L. Screening for Antifibrotic Compounds Using High Throughput System Based on Fluorescence Polarization. Biology 2014, 3, 281-294.

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