Vol 3: Screening for Antifibrotic Compounds Using High Throughput System Based on Fluorescence Polarization.Reportar como inadecuado



 Vol 3: Screening for Antifibrotic Compounds Using High Throughput System Based on Fluorescence Polarization.


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This article is from Biology, volume 3.AbstractFibroproliferative 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 α1I mRNA and α2I mRNA encode for type I collagen and they have a unique 5 stem-loop structure in their 5 untranslated regions 5SL. Collagen 5SL binds protein LARP6 with high affinity and specificity. The interaction between LARP6 and the 5SL 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 5SL 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.



Autor: Stefanovic, Branko; Stefanovic, Lela

Fuente: https://archive.org/







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