title: Preparation and characterization of vorinostat-coated beads for profiling of novel target proteins.
abstract: 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.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology & Department of Chemistry, Nankai University, Tianjin 300071, PR China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology & Department of Chemistry, Nankai University, Tianjin 300071, PR China; Department of Biochemistry and Molecular Biology & Tianjin Key Laboratory of Medical Epigenetics, Basic Medical School, Tianjin Medical University, Tianjin 300070, PR China. Electronic address: zhangkai@nankai.edu.cn.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: The Chemical Proteomics Center and State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Chemical Proteomics Center and State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors.forename: Minjia
authors.initials: M
authors.lastname: Tan
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology & Department of Chemistry, Nankai University, Tianjin 300071, PR China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology & Department of Chemistry, Nankai University, Tianjin 300071, PR China.
authors.forename: Xiwen
authors.initials: X
authors.lastname: He
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology & Department of Chemistry, Nankai University, Tianjin 300071, PR China; National Chromatographic Research and Analysis Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, PR China.
authors.forename: Yukui
authors.initials: Y
authors.lastname: Zhang
keywords: Chemical probe; HPLC–MS/MS; Proteomics; Target proteins; Vorinostat