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Title: Activation Of P300 Histone Acetyltransferase By Small Molecules Altering Enzyme Structure: Period Probed By Surface Enhanced Raman Spectroscopy
Authors: Mantelingu, K
Kishore, A Hari
Balasubramanyam, K
Kumar, G V Pavan
Altaf, M
Swamy, S Nanjunda
Selvi, Ruthrotha
Das, Chandrima
Narayana, Chandrabhas
Rangappa, K S
Kundu, Tapas K
Keywords: Anacardic Acids-chemistry
Cell Cycle Proteins-chemistry
Cell Cycle Proteins-metabolism
Enzyme Activation-drug effects
HeLa Cells
Histone Acetyltransferases-chemistry
Histone Acetyltransferases-metabolism
Molecular Structure
Salicylic Acid-chemistry
Spectrum Analysis
Transcription Factors-chemistry
Transcription Factors-metabolism
p300-CBP Transcription Factors
Issue Date: 3-May-2007
Publisher: American Chemical Society
Citation: Journal of Physical Chemistry B 111(17), 4527-4534 (2007)
Abstract: Reversible acetylation of nucleosomal histones and nonhistone proteins play pivotal roles in the regulation of all the DNA templated phenomenon. Dysfunction of the enzymes involved in the acetylation/deacetylation leads to several diseases. Therefore, these enzymes are the targets for new generation therapeutics. Here, we report the synthesis of trifluoromethyl phenyl benzamides and their effect on histone acetyltransferase (HAT) activity of p300. One of these benzamides, CTPB (N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-6-pentadecyl-benzamide), was discovered as a potent activator of the p300 HAT activity. We have found that pentadecyl hydrocarbon chain of CTPB is required to activate the HAT only under certain context. Furthermore, our results show that the relative position of −CF3 and −Cl in CTB (N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-benzamide) is also very critical for the activation. Surface-enhanced Raman spectroscopy (SERS) of p300 and the HAT activator complexes evidently suggest that the activation of HAT activity is achieved by the alteration of p300 structure. Therefore, apart from elucidating the chemical basis for small molecule mediated activation of p300, this report also describes, for the first time, Raman spectroscopic analysis of the complexes of histone-modifying enzymes and their modulators, which may be highly useful for therapeutic applications.
Description: Restricted Access
Other Identifiers: 1520-6106
Appears in Collections:Research Papers (Tapas K. Kundu)

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