High-throughput identification of inhibitors of human mitochondrial peptide deformylase Journal Article


Authors: Antczak, C.; Shum, D.; Escobar, S.; Bassit, B.; Kim, E.; Seshan, V. E.; Wu, N.; Yang, G.; Ouerfelli, O.; Li, Y. M.; Scheinberg, D. A.; Djaballah, H.
Article Title: High-throughput identification of inhibitors of human mitochondrial peptide deformylase
Abstract: The human mitochondrial peptide deformylase (HsPDF) provides a potential new target for broadly acting antiproliferative agents. To identify novel nonpeptidomimetic and nonhydroxamic acid-based inhibitors of HsPDF, the authors have developed a high-throughput screening (HTS) strategy using a fluorescence polarization (FP)-based binding assay as the primary assay for screening chemical libraries, followed by an enzymatic-based assay to confirm hits, prior to characterization of their antiproliferative activity against established tumor cell lines. The authors present the results and performance of the established strategy tested in a pilot screen of 2880 compounds and the identification of the 1st inhibitors. Two common scaffolds were identified within the hits. Furthermore, cytotoxicity studies revealed that most of the confirmed hits have antiproliferative activity. These findings demonstrate that the designed strategy can identify novel functional inhibitors and provide a powerful alternative to the use of functional assays in HTS and support the hypothesis that HsPDF inhibitors may constitute a new class of antiproliferative agent. © 2007 Society for Biomolecular Sciences.
Keywords: controlled study; unclassified drug; human cell; drug activity; enzyme inhibition; embryo; cell line; antineoplastic activity; cytotoxicity; high throughput screening; fluorescence polarization; drug mechanism; enzyme inhibitors; tumor cell line; hematoxylin; epigallocatechin gallate; peptide deformylase; actinonin; amidohydrolases; mitochondria; mitochondrion; enzyme assay; jurkat cells; high-throughput screening; k562 cells; peptide deformylase inhibitor; binding assay; antiproliferative agents; human peptide deformylase; spectrometry, mass, electrospray ionization; hl-60 cells; 2',2' bisepigallocatechin monogallate; 3 methoxycatechol; 7,8 dihydroxyflavone; chloranil; epitheaflavin monogallate; gallic acid derivative; hematin; human mitochondrial peptide deformylase; irigenol; purpurin derivative; purpurogallin; pyrogallol; quinalizarin; theaflavin; thiram; fluorescence polarization immunoassay
Journal Title: Journal of Biomolecular Screening
Volume: 12
Issue: 4
ISSN: 1087-0571
Publisher: Sage Publications  
Date Published: 2007-06-01
Start Page: 521
End Page: 535
Language: English
DOI: 10.1177/1087057107300463
PUBMED: 17435169
PROVIDER: scopus
PMCID: PMC2234356
DOI/URL:
Notes: --- - "Cited By (since 1996): 15" - "Export Date: 17 November 2011" - "CODEN: JBISF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Venkatraman Ennapadam Seshan
    288 Seshan
  2. Nian Wu
    30 Wu
  3. Guangli Yang
    21 Yang
  4. Christophe Antczak
    40 Antczak
  5. Yueming Li
    104 Li
  6. David Shum
    52 Shum
  7. Bhramdeo Bassit
    7 Bassit
  8. Earl Kim
    2 Kim