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Solvent-induced protein precipitation for drug target discovery on proteomic scale.

07:00 EST 3rd December 2019 | BioPortfolio

Summary of "Solvent-induced protein precipitation for drug target discovery on proteomic scale."

High-throughput drug discovery is highly depended on the targets available to accelerate the process of candidates screening. Traditional chemical proteomics approaches for the screening of drug targets usually require the immobilization/modification of the drug molecules to pull down the interacting proteins. Recently energetics-based proteomics methods provide an alternative way to study drug-protein interaction by using complex cell lysate directly without any modification of the drugs. In this study, we developed a novel energetics-based proteomics strategy, solvent-induced protein precipitation (SIP) approach, to profile the interaction of drugs with their target proteins by using quantitative proteomics. The method is easy to use for any laboratory with common chemical reagents of acetone, alcohol and acetic acid. The SIP approach was able to identify the well-known protein targets of methotrexate, SNS-032 and a pan-kinase inhibitor of staurosporine in cell lysate. We further applied this approach to discover the off-targets of geldanamycin. Three known protein targets of HSP90 family were successfully identified, and several potential off-targets including NADH dehydrogenase subunits NDUFV1 and NDUFAB1 were identified for the first time, and the NDUFV1 was validated by using western blotting. In addition, this approach was capable of evaluating affinity of drug-target interaction. The data collectively proved that our approach provides a powerful platform for drug target discovery.

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Name: Analytical chemistry
ISSN: 1520-6882
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