|Accumulation of excess protein is linked to aging, Parkinson's disease, and other human diseases. The large enzyme complex known as the proteasome, specifically its subunit the 20S core particle (20S CP), can degrade proteins to then be recycled to make new proteins. Scientists hypothesize that chemically stimulating the 20S CP can degrade the disease-related proteins and serve as a treatment for protein accumulation disorders. The reporter molecule currently available to assay new compounds for 20S CP-stimulating activity produces a high level of background signal in the absence of any stimulators, making discovery of new 20S CP stimulators via high-throughput screening a challenge.
Researchers at Purdue University have designed a new reporter molecule to detect stimulation of the 20S CP that is 3.5 times as sensitive as the current reporter. The sensitivity and effectiveness of this new FRET-based reporter was validated by screening 715 compounds for 20S CP stimulating activity. Four 20S CP stimulators were found in the screen, two of which were missed in a screen using the established reporter molecule.
Rachel A. Coleman and Darci J. Trader, Developement and Application of a Sensitive Peptide Reporter to DIscover 20S Proteasome Stimulators
ACS Comb. Sci., DOI: 10.1021/acscombsci.7b00193
-Amenable to high-throughput drug screening
-Parkinson's disease drug discovery
Sep 12, 2018
Sep 15, 2017
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