Design, synthesis, and biological evaluation of a small-molecule inhibitor of the histone acetyltransferase Gcn5

被引：130

作者：

Biel, M

Kretsovali, A

Karatzali, E

Papamatheakis, J

Giannis, A

机构：

[1] FORTH, Vassilika Vouton, Inst Mol Biol & Biotechnol, Iraklion, Greece

[2] Univ Leipzig, Inst Organ Chem, D-04103 Leipzig, Germany

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2004年 / 43卷 / 30期

关键词：

biological activity; epigenetics; histone acetyltransferase; histone code; inhibitors;

D O I：

10.1002/anie.200453879

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

HATs off! The development of the first cell-permeable small-molecule inhibitor of the human histone acetyltransferase (HAT) Gcn5 opens up new possibilities for understanding the histone code. Based on kinetic data and the proposed mechanism of the acetylation by Gcn5, the relatively simple butyrolactone structure of the inhibitor was identified.

引用

收藏

页码：3974 / 3976

页数：3

相关论文

共 27 条

[1] Small molecule modulators of histone acetyltransferase p300 [J].

Balasubramanyam, K ;

Swaminathan, V ;

Ranganathan, A ;

Kundu, TK .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (21) :19134-19140

[2] Histone modifications in transcriptional regulation [J].

Berger, SL .

CURRENT OPINION IN GENETICS & DEVELOPMENT, 2002, 12 (02) :142-148

[3] DIRECT METHODS FOR ALPHA-METHYLENE LACTONE SYNTHESIS USING ITACONIC ACID-DERIVATIVES [J].

CARLSON, RM ;

OYLER, AR .

JOURNAL OF ORGANIC CHEMISTRY, 1976, 41 (26) :4065-4069

[4] The diverse functions of histone acetyltransferase complexes [J].

Carrozza, MJ ;

Utley, RT ;

Workman, JL ;

Côté, J .

TRENDS IN GENETICS, 2003, 19 (06) :321-329

[5] PHOSPHORYLATED CREB BINDS SPECIFICALLY TO THE NUCLEAR-PROTEIN CBP [J].

CHRIVIA, JC ;

KWOK, RPS ;

LAMB, N ;

HAGIWARA, M ;

MONTMINY, MR ;

GOODMAN, RH .

NATURE, 1993, 365 (6449) :855-859

[6] Histone modification: the 'next wave' in cancer therapeutics [J].

Chung, D .

TRENDS IN MOLECULAR MEDICINE, 2002, 8 (04) :S10-S11

[7] Synthesis and antiproliferative activity of a new compound containing an α-methylene-γ-lactone group [J].

González, AG ;

Silva, MH ;

Padrón, JI ;

León, F ;

Reyes, E ;

Alvarez-Mon, M ;

Pivel, JP ;

Quintana, J ;

Estévez, F ;

Bermejo, J .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (12) :2358-2361

[8]

Hoffmann H. M. R., 1985, ANGEW CHEM, V97, P96

[9] SYNTHESIS AND BIOLOGICAL-ACTIVITY OF ALPHA-METHYLENE-GAMMA-BUTYROLACTONES [J].

HOFFMANN, HMR ;

RABE, J .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH, 1985, 24 (02) :94-110

[10] Small molecules as inhibitors of cyclin-dependent kinases [J].

Huwe, A ;

Mazitschek, R ;

Giannis, A .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2003, 42 (19) :2122-2138