HATs off: Selective synthetic inhibitors of the histone acetyltransferases p300 and PCAF

Ontario D. Lau; Tapas K. Kundu; Raymond E. Soccio; Slimane Ait-Si-Ali; Ehab M. Khalil; Alex Vassilev; Alan P. Wolffe; Yoshihiro Nakatani; Robert G. Roeder; Philip A. Cole

doi:10.1016/s1097-2765(00)80452-9

HATs off: Selective synthetic inhibitors of the histone acetyltransferases p300 and PCAF

Ontario D. Lau, Tapas K. Kundu, Raymond E. Soccio, Slimane Ait-Si-Ali, Ehab M. Khalil, Alex Vassilev, Alan P. Wolffe, Yoshihiro Nakatani, Robert G. Roeder, Philip A. Cole

Research output: Contribution to journal › Article › peer-review

326 Scopus citations

Abstract

Histone acetyltransferases (HATs) play important roles in the regulation of gene expression. In this report, we describe the design, synthesis, and application of peptide CoA conjugates as selective HAT inhibitors for the transcriptional coactivators p300 and PCAF. Two inhibitors (Lys-CoA for p300 and H3-CoA-20 for PCAF) were found to be potent (IC₅₀ almost equal to 0.5 μM) and selective (~200-fold) in blocking p300 and PCAF HAT activities. These inhibitors were used to probe enzymatic and transcriptional features of HAT function in several assay systems. These compounds should be broadly useful as biological tools for evaluating the roles of HATs in transcriptional studies and may serve as lead agents for the development of novel antineoplastic therapeutics.

Original language	English (US)
Pages (from-to)	589-595
Number of pages	7
Journal	Molecular cell
Volume	5
Issue number	3
DOIs	https://doi.org/10.1016/s1097-2765(00)80452-9
State	Published - 2000
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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@article{b512a9aa14f741b9af90bf854cb4ce8e,

title = "HATs off: Selective synthetic inhibitors of the histone acetyltransferases p300 and PCAF",

abstract = "Histone acetyltransferases (HATs) play important roles in the regulation of gene expression. In this report, we describe the design, synthesis, and application of peptide CoA conjugates as selective HAT inhibitors for the transcriptional coactivators p300 and PCAF. Two inhibitors (Lys-CoA for p300 and H3-CoA-20 for PCAF) were found to be potent (IC50 almost equal to 0.5 μM) and selective (~200-fold) in blocking p300 and PCAF HAT activities. These inhibitors were used to probe enzymatic and transcriptional features of HAT function in several assay systems. These compounds should be broadly useful as biological tools for evaluating the roles of HATs in transcriptional studies and may serve as lead agents for the development of novel antineoplastic therapeutics.",

author = "Lau, {Ontario D.} and Kundu, {Tapas K.} and Soccio, {Raymond E.} and Slimane Ait-Si-Ali and Khalil, {Ehab M.} and Alex Vassilev and Wolffe, {Alan P.} and Yoshihiro Nakatani and Roeder, {Robert G.} and Cole, {Philip A.}",

note = "Funding Information: We thank Zhengxin Wang for recombinant human TopoI, and Lee Kraus and James Kadonaga for the baculovirus p300 expression vector. We thank the NIH Medical Scientist Training Program (R. E. S.), Burroughs Wellcome Fund (E. M. K.), EMBO (Long-Term Fellowship to S. A.), Ellison Medical Foundation (P. A. C.), and NCI (CA42567) to R. G. R. for financial support.",

year = "2000",

doi = "10.1016/s1097-2765(00)80452-9",

language = "English (US)",

volume = "5",

pages = "589--595",

journal = "Molecular cell",

issn = "1097-2765",

publisher = "Cell Press",

number = "3",

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TY - JOUR

T1 - HATs off

T2 - Selective synthetic inhibitors of the histone acetyltransferases p300 and PCAF

AU - Lau, Ontario D.

AU - Kundu, Tapas K.

AU - Soccio, Raymond E.

AU - Ait-Si-Ali, Slimane

AU - Khalil, Ehab M.

AU - Vassilev, Alex

AU - Wolffe, Alan P.

AU - Nakatani, Yoshihiro

AU - Roeder, Robert G.

AU - Cole, Philip A.

N1 - Funding Information: We thank Zhengxin Wang for recombinant human TopoI, and Lee Kraus and James Kadonaga for the baculovirus p300 expression vector. We thank the NIH Medical Scientist Training Program (R. E. S.), Burroughs Wellcome Fund (E. M. K.), EMBO (Long-Term Fellowship to S. A.), Ellison Medical Foundation (P. A. C.), and NCI (CA42567) to R. G. R. for financial support.

PY - 2000

Y1 - 2000

N2 - Histone acetyltransferases (HATs) play important roles in the regulation of gene expression. In this report, we describe the design, synthesis, and application of peptide CoA conjugates as selective HAT inhibitors for the transcriptional coactivators p300 and PCAF. Two inhibitors (Lys-CoA for p300 and H3-CoA-20 for PCAF) were found to be potent (IC50 almost equal to 0.5 μM) and selective (~200-fold) in blocking p300 and PCAF HAT activities. These inhibitors were used to probe enzymatic and transcriptional features of HAT function in several assay systems. These compounds should be broadly useful as biological tools for evaluating the roles of HATs in transcriptional studies and may serve as lead agents for the development of novel antineoplastic therapeutics.

AB - Histone acetyltransferases (HATs) play important roles in the regulation of gene expression. In this report, we describe the design, synthesis, and application of peptide CoA conjugates as selective HAT inhibitors for the transcriptional coactivators p300 and PCAF. Two inhibitors (Lys-CoA for p300 and H3-CoA-20 for PCAF) were found to be potent (IC50 almost equal to 0.5 μM) and selective (~200-fold) in blocking p300 and PCAF HAT activities. These inhibitors were used to probe enzymatic and transcriptional features of HAT function in several assay systems. These compounds should be broadly useful as biological tools for evaluating the roles of HATs in transcriptional studies and may serve as lead agents for the development of novel antineoplastic therapeutics.

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DO - 10.1016/s1097-2765(00)80452-9

M3 - Article

C2 - 10882143

AN - SCOPUS:0033714888

SN - 1097-2765

VL - 5

SP - 589

EP - 595

JO - Molecular cell

JF - Molecular cell

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ER -

HATs off: Selective synthetic inhibitors of the histone acetyltransferases p300 and PCAF

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