Document Detail


Pharmacodynamic assessment of histone deacetylase inhibitors: infrared vibrational spectroscopic imaging of protein acetylation.
MedLine Citation:
PMID:  18651756     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Infrared spectroscopy identifies molecules by detection of vibrational patterns characteristic of molecular bonds. We apply this approach to measure protein acetylation after treatment with histone deacetylase inhibitors. The anticancer activity of histone deacetylase inhibitors (HDACi) is ascribed to the hyperacetylation of both core nucleosomal histones and nonhistone proteins critical to the maintenance of the malignant phenotype (Marks, P. A.; Richon, V. M.; Breslow, R.; Rifkind, R. A. Curr. Opin. Oncol. 2001, 13, 477-483; Mai, A.; Massa, S.; Rotili, D.; Cerbara, I.; Valente, S.; Pezzi, R.; Simeoni, S.; Ragno, R. Med. Res. Rev. 2005, 25, 261-309). After incubation of the peripheral blood mononuclear cells (PBMCs) in vitro with the HDACi SNDX-275, a benzamide drug derivative, vibrational spectral changes in the methyl and methylene stretching mode regions, which reflect concentration-dependent increases in protein acetylation, were detected and quantified. We applied these metrics, based upon spectral differences, to peripheral blood mononuclear cells from patients treated in vivo with this agent. The data demonstrate a new approach to a sensitive assessment of global molecular modifications that is independent of antibodies, requires minimal cell processing, and is easily adapted to high-throughput screening.
Authors:
Tsoching Chen; Min-Jung Lee; Yeong Sang Kim; Sunmin Lee; Shivaani Kummar; Martin Gutierrez; Stephen M Hewitt; Jane B Trepel; Ira W Levin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2008-07-24
Journal Detail:
Title:  Analytical chemistry     Volume:  80     ISSN:  1520-6882     ISO Abbreviation:  Anal. Chem.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-08-15     Completed Date:  2008-10-09     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  0370536     Medline TA:  Anal Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6390-6     Citation Subset:  IM    
Affiliation:
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetylation
Benzamides / pharmacology*
Cells, Cultured
Diagnostic Imaging / methods*
Enzyme Inhibitors / pharmacology*
Histone Deacetylase Inhibitors*
Histone Deacetylases / chemistry*,  metabolism
Humans
Leukocytes, Mononuclear / cytology*
Pyridines / pharmacology*
Spectroscopy, Fourier Transform Infrared / methods*
Vibration
Grant Support
ID/Acronym/Agency:
Z01 DK029065-01/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Benzamides; 0/Enzyme Inhibitors; 0/Histone Deacetylase Inhibitors; 0/Pyridines; 0/entinostat; EC 3.5.1.98/Histone Deacetylases
Comments/Corrections

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