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Identification of Potent Inhibitors against Human Peptide Deformylase as Anticancer Agents
Identification of Potent Inhibitors against Human Peptide Deformylase as Anticancer Agents
Bulletin of the Korean Chemical Society. 2013. Dec, 34(12): 3885-3887
Copyright © 2013, Korea Chemical Society
  • Received : August 30, 2013
  • Accepted : September 16, 2013
  • Published : December 20, 2013
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About the Authors
Sang Jae Lee
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea
Ok Sung Jung
School of Systems Biomedical Science, Soongsil University, Seoul 156-743, Korea
Bong-Jin Lee
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea
Kwang-Hwi Cho
School of Systems Biomedical Science, Soongsil University, Seoul 156-743, Korea
Byung Il Lee
Research Institute, National Cancer Center, Goyang, Gyeonggi 410-769, Korea

Abstract
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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 ). 19 20 Human PDF were purified according to previously reported method18 and biochemical PDF assays were performed closely followed by previous studies. 13 The IC 50 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 × 10 4 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.
Acknowledgements
This work was supported by a National Cancer Center Research Grant (1310400) from the National Cancer Center in Korea
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