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

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

*  and
Received: 15 January 2014; in revised form: 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.
Keywords: fibrosis; antifibrotic drugs; RNA binding protein; fluorescence polarization fibrosis; antifibrotic drugs; RNA binding protein; fluorescence polarization
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Stefanovic, B.; Stefanovic, L. Screening for Antifibrotic Compounds Using High Throughput System Based on Fluorescence Polarization. Biology 2014, 3, 281-294.

AMA Style

Stefanovic B, Stefanovic L. Screening for Antifibrotic Compounds Using High Throughput System Based on Fluorescence Polarization. Biology. 2014; 3(2):281-294.

Chicago/Turabian Style

Stefanovic, Branko; Stefanovic, Lela. 2014. "Screening for Antifibrotic Compounds Using High Throughput System Based on Fluorescence Polarization." Biology 3, no. 2: 281-294.


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