کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1199577 | 1493554 | 2014 | 8 صفحه PDF | دانلود رایگان |
• A vorinostat-based small molecule probe was designed, synthesized and immobilized onto the surface of sepharose beads.
• Vorinosta-coated beads based proteomics approach for profiling of novel target proteins of vorinostat.
• ENO-1 was detected and confirmed as a novel, potential target of vorinostat.
Inhibitors of histone deacetylases (HDACs) have been considered to be new anticancer agents. As a key inhibitor of HDAC, vorinostat can cause growth arrest and death of a broad of transformed cells and interact with a variety of substrates. A comprehensive analysis of proteins interacting with HDAC inhibitors is of great importance in understanding molecular mechanisms of the drugs. Here, we reported the preparation and characterization of vorinostat-coated beads for profiling of novel target proteins of vorinostat (a key HDAC inhibitor). The enriched proteins were further analyzed by HPLC–MS/MS. Besides the known substrates, there were also several novel enriched protein candidates, one of which was a metalloenzyme α-enolase (ENO-1). According to our best knowledge, it is the first time that ENO-1 has been detected as a potential target of vorinostat through chemoproteomics approach. Further competition analysis indicated that ENO-1 may be co-enriched as a substrate complex. Our results demonstrated that the chemical probe combined with proteomics approach may be developed as a potential tool to identify target proteins of drugs.
Journal: Journal of Chromatography A - Volume 1372, 12 December 2014, Pages 34–41