Tautomeric modification of GlcNAc-thiazoline

被引：36

作者：

Knapp, Spencer

Abdo, Mohannad

Ajayi, Kehinde

Huhn, Richard A.

Emge, Thomas J.

Kim, Eun Ju

Hanover, John A.

机构：

[1] Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA

[2] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA

来源：

ORGANIC LETTERS | 2007年 / 9卷 / 12期

关键词：

D O I：

10.1021/ol0706814

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The potent O-GlcNAcase (OGA) inhibitor GlcNAc-thiazoline has been modified by buffer- or acylation-induced imine-to-enamine conversion and then electrophile or radical addition (X-n = D-3, F, N-3, OH, SMe, COCF3, CF3). Several functionalized GlcNAc-thiazolines show highly selective inhibition of OGA vs human hexosaminidase and thus have promise as tools for targeted investigations of OGA, an enzyme linked to diabetes and neurodegeneration. A new radical addition/fragmentation reaction of the N-(trifluoroacetyl)enamine has been discovered.

引用

收藏

页码：2321 / 2324

页数：4

相关论文

共 34 条

[1] The microtubule-associated protein tau is extensively modified with O-linked N-acetylglucosamine [J].

Arnold, CS ;

Johnson, GVW ;

Cole, RN ;

Dong, DLY ;

Lee, M ;

Hart, GW .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (46) :28741-28744

[2] REACTION OF 2,6-DIMETHYLPYRIDINE AND 2,4,6-TRIMETHYLPYRIDINE WITH TRIFLUOROMETHANESULFONIC ANHYDRIDE [J].

BINKLEY, RW ;

AMBROSE, MG .

JOURNAL OF ORGANIC CHEMISTRY, 1983, 48 (10) :1776-1777

[3]

BOGNAR R, 1979, LIEBIGS ANN CHEM, P701

[4] SOME FREE-RADICAL ADDITION REACTIONS OF NORBORNENE AND RELATED COMPOUNDS [J].

DAVIES, DI ;

PARFITT, LT ;

ALDEN, CK ;

CLAISSE, JA .

JOURNAL OF THE CHEMICAL SOCIETY C-ORGANIC, 1969, (11) :1585-&

[5] Structure and mechanism of a bacterial β-glucosaminidase having O-GlcNAcase activity [J].

Dennis, RJ ;

Taylor, EJ ;

Macauley, MS ;

Stubbs, KA ;

Turkenburg, JP ;

Hart, SJ ;

Black, GN ;

Vocadlo, DJ ;

Davies, GJ .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2006, 13 (04) :365-371

[6] GlcNAcstatin:: A picomolar, selective O-GlcNAcase inhibitor that modulates intracellular O-GlcNAcylation levels [J].

Dorfmueller, Helge C. ;

Borodkin, Vladimir S. ;

Schimpl, Marianne ;

Shepherd, Sharon M. ;

Shpiro, Natalia A. ;

van Aalten, Daan M. F. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2006, 128 (51) :16484-16485

[7] CONFORMATION OF 3,4,6-TRI-O-ACETYL-1,2-DIDEOXY-ALPHA-D-GLUCOPYRANO-[2,1-D]-2-OXAZOLINES [J].

FOCESFOCES, C ;

CANO, FH ;

BERNABE, M ;

PENADES, S ;

MARTINLOMAS, M .

CARBOHYDRATE RESEARCH, 1984, 135 (01) :1-11

[8] ACETYLATION OF 2-METHYL-DELTA-2-THIAZOLINE .2. FORMATION AND PROPERTIES OF 2-METHYLENE-3-ACETYLTHIAZOLIDINE [J].

GROBOVSKY, LV ;

SCHMIR, GL .

TETRAHEDRON, 1971, 27 (06) :1185-+

[9] An O-GlcNAcase-specific inhibitor and substrate engineered by the extension of the N-acetyl moiety [J].

Kim, EJ ;

Perreira, M ;

Thomas, CJ ;

Hanover, JA .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2006, 128 (13) :4234-4235

[10] Enzymatic characterization of O-GlcNAcase isoforms using a fluorogenic GlcNAc substrate [J].

Kim, Eun Ju ;

Kang, Dae Ook ;

Love, Dona C. ;

Hanover, John A. .

CARBOHYDRATE RESEARCH, 2006, 341 (08) :971-982

← 1 2 3 4 →