Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Identification of Potent Inhibitors against Human Peptide Deformylase as Anticancer Agents

  • Lee, Sang Jae (Research Institute, National Cancer Center) ;
  • Jung, Ok Sung (School of Systems Biomedical Science, Soongsil University) ;
  • Lee, Bong-Jin (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University) ;
  • Cho, Kwang-Hwi (School of Systems Biomedical Science, Soongsil University) ;
  • Lee, Byung Il (Research Institute, National Cancer Center)
  • Received : 2013.08.30
  • Accepted : 2013.09.16
  • Published : 2013.12.20
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Abstract

Keywords

Experimental Methods

Chemistry and Measurement of PDF Activity. The inhibitors hydroxamate/peptidomimetic [PMT387 (7a) and PMT497] and the reverse hydroxamate/nonpeptide scaffold inhibitors [PMT1039 (15e) and PMT1067] were synthesized and supplied by ProMediTech (Figure 1).1920 Human PDF were purified according to previously reported method18 and biochemical PDF assays were performed closely followed by previous studies.13 The IC50 value was calculated using nonlinear regression and GraphPad Prism 5.

In vitro Cell-based Chemosensitivity Assay. Cancer cells were cultured in RPMI 1640 containing 10% fetal calf serum, 100 U/mL penicillin, 100 μg/mL streptomycin, and 2 mM ʟ-glutamine (complete RPMI medium). All cancer cells were plated at 1 × 104 cells per well in a 96 well plate. Drugs of different concentrations were then added. The sulforhod-amine B assay is used for cell density determination, based on the measurement of cellular protein content.17

Molecular Docking Study. The binding modes of four inhibitors to human PDF (3G5P)18 were predicted using AutoDokc-Vina.21 One cobalt ion and the flexibility of side chains of the amino acids in the active site were considered.

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