Pharmacodynamic assessment of histone deacetylase inhibitors: Infrared vibrational spectroscopic imaging of protein acetylation

被引：21

作者：

Chen, Tsoching ^{[1
]}

Lee, Min-Jung ^{[2
]}

Kim, Yeong Sang ^{[2
]}

Lee, Sunmin ^{[2
]}

Kummar, Shivaani ^{[3
]}

Gutierrez, Martin ^{[3
]}

Hewitt, Stephen M. ^{[3
]}

Trepel, Jane B. ^{[2
]}

Levin, Ira W. ^{[1
]}

机构：

[1] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA

[2] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[3] NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA

来源：

ANALYTICAL CHEMISTRY | 2008年 / 80卷 / 16期

关键词：

D O I：

10.1021/ac800840y

中图分类号：

O65 [分析化学];

学科分类号：

070302 ; 081704 ;

摘要：

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.

引用

页码：6390 / 6396

页数：7

共 28 条

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