Enzymatic Site-Specific Functionalization of Protein Methyltransferase Substrates with Alkynes for Click Labeling

被引：102

作者：

Peters, Wibke ^{[1
,2
]}

Willnow, Sophie ^{[1
]}

Duisken, Mike ^{[3
]}

Kleine, Henning ^{[2
]}

Macherey, Thomas ^{[1
]}

Duncan, Kelly E. ^{[4
]}

Litchfield, David W. ^{[4
]}

Luescher, Bernhard ^{[2
]}

Weinhold, Elmar ^{[1
]}

机构：

[1] Rhein Westfal TH Aachen, Inst Organ Chem, D-52056 Aachen, Germany

[2] Rhein Westfal TH Aachen, Inst Biochem & Mol Biol, Sch Med, D-52074 Aachen, Germany

[3] Leco Instruments GmbH, Monchengladbach, Germany

[4] Univ Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON, Canada

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2010年 / 49卷 / 30期

基金：

加拿大健康研究院;

关键词：

click chemistry; cofactors; epigenetics; proteins; transferases; LYSINE METHYLTRANSFERASE; H3K4; TRIMETHYLATION; TERMINAL ALKYNES; HISTONE H3R2; METHYLATION; COMPLEX; DNA; COFACTORS; TARGETS; AZIDES;

D O I：

10.1002/anie.201001240

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Pass and click: Protein methylation is an important posttranslational modification. Because the methyl group is a poor reporter group, new methods are needed to analyze methyltransferase substrates. A S-adenosyl-L-methioninebased cofactor was synthesized and used for the sitespecific functionalization of proteins with alkynes by methyltransferases (first step) and subsequent labeling through CuAAC click chemistry (second step; see scheme). (Figure Presented). © 2010 Wiley-VCH Verlag GmbH & Co.KGaA.

引用

页码：5170 / 5173

页数：4

共 30 条

[1] The complex language of chromatin regulation during transcription [J].

Berger, Shelley L. .

NATURE, 2007, 447 (7143) :407-412

[2] Azide-alkyne coupling:: A powerful reaction for bioconjugate chemistry [J].

Breinbauer, R ;

Köhn, M .

CHEMBIOCHEM, 2003, 4 (11) :1147-1149

[3] Direct transfer of extended groups from synthetic cofactors by DNA methyltransferases [J].

Dalhoff, C ;

Lukinavicius, G ;

Klimasauskas, S ;

Weinhold, E .

NATURE CHEMICAL BIOLOGY, 2006, 2 (01) :31-32

[4] Synthesis of S-adenosyl-L-methionine analogs and their use for sequence-specific transalkylation of DNA by methyltransferases [J].

Dalhoff, Christian ;

Lukinavicius, Grazvydas ;

Klimasauakas, Saulius ;

Weinhold, Elmar .

NATURE PROTOCOLS, 2006, 1 (04) :1879-1886

[5] Methylation of histone H3R2 by PRMT6 and H3K4 by an MLL complex are mutually exclusive [J].

Guccione, Ernesto ;

Bassi, Christian ;

Casadio, Fabio ;

Martinato, Francesca ;

Cesaroni, Matteo ;

Schuchlautz, Henning ;

Luescher, Bernhard ;

Amati, Bruno .

NATURE, 2007, 449 (7164) :933-U18

[6] Finding thresholds of risk for components of the pediatric metabolic syndrome [J].

Huang, Terry T-K .

JOURNAL OF PEDIATRICS, 2008, 152 (02) :158-159

[7] PRMT6-mediated methylation of R2 in histone H3 antagonizes H3K4 trimethylation [J].

Hyllus, Dawin ;

Stein, Claudia ;

Schnabel, Kristin ;

Schiltz, Emile ;

Imhof, Axel ;

Dou, Yali ;

Hsieh, James ;

Bauer, Uta-Maria .

GENES & DEVELOPMENT, 2007, 21 (24) :3369-3380

[8] Arginine methylation at histone H3R2 controls deposition of H3K4 trimethylation [J].

Kirmizis, Antonis ;

Santos-Rosa, Helena ;

Penkett, Christopher J. ;

Singer, Michael A. ;

Vermeulen, Michiel ;

Mann, Matthias ;

Baehler, Juerg ;

Green, Roland D. ;

Kouzarides, Tony .

NATURE, 2007, 449 (7164) :928-U17

[9] Regulation of histone methylation by demethylimination and demethylation [J].

Klose, Robert J. ;

Yi Zhang .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2007, 8 (04) :307-318

[10] Chromatin modifications and their function [J].

Kouzarides, Tony .

CELL, 2007, 128 (04) :693-705

← 1 2 3 →