OGA inhibition by GlcNAc-selenazoline

Eun Ju Kim; Dona C. Love; Etzer Darout; Mohannad Abdo; Brian Rempel; Stephen G. Withers; Paul R. Rablen; John A. Hanover; Spencer Knapp

doi:10.1016/j.bmc.2010.08.010

OGA inhibition by GlcNAc-selenazoline

Eun Ju Kim, Dona C. Love, Etzer Darout, Mohannad Abdo, Brian Rempel, Stephen G. Withers, Paul R. Rablen, John A. Hanover, Spencer Knapp

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

20 Scopus citations

Abstract

The title compound, which differs from the powerful O-GlcNAcase (OGA) inhibitor GlcNAc-thiazoline only at the chalcogen atom (Se for S), is a much weaker inhibitor in a direct OGA assay. In human cells, however, the selenazoline shows comparable ability to induce hyper-O-GlcNAc-ylation, and the two show similar reduction of insulin-stimulated translocation of glucose transporter 4 in differentiated 3T3 adipocytes.

Original language	English (US)
Pages (from-to)	7058-7064
Number of pages	7
Journal	Bioorganic and Medicinal Chemistry
Volume	18
Issue number	19
DOIs	https://doi.org/10.1016/j.bmc.2010.08.010
State	Published - Oct 1 2010

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Keywords

Hyperglycemia
Lipophilicity
N-Acetylhexosaminidase
Post-translational modification
Transcription factor
Transition state
Woollins reagent

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10.1016/j.bmc.2010.08.010

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title = "OGA inhibition by GlcNAc-selenazoline",

abstract = "The title compound, which differs from the powerful O-GlcNAcase (OGA) inhibitor GlcNAc-thiazoline only at the chalcogen atom (Se for S), is a much weaker inhibitor in a direct OGA assay. In human cells, however, the selenazoline shows comparable ability to induce hyper-O-GlcNAc-ylation, and the two show similar reduction of insulin-stimulated translocation of glucose transporter 4 in differentiated 3T3 adipocytes.",

keywords = "Hyperglycemia, Lipophilicity, N-Acetylhexosaminidase, Post-translational modification, Transcription factor, Transition state, Woollins reagent",

author = "Kim, {Eun Ju} and Love, {Dona C.} and Etzer Darout and Mohannad Abdo and Brian Rempel and Withers, {Stephen G.} and Rablen, {Paul R.} and Hanover, {John A.} and Spencer Knapp",

note = "Funding Information: We are grateful to NIH ( SK, AI055760 ) and the Henry Dreyfus Teacher-Scholar Awards Program (P.R.R.) for partial financial support, UNCF-Merck for a graduate fellowship to E.D., the Canadian Institutes for Health Research and the Natural Science and Engineering Research Council (S.G.W. and B.R.), the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH (J.A.H.), and the National Research Foundation of Korea ( EJK, 20090065 ). ",

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doi = "10.1016/j.bmc.2010.08.010",

language = "English (US)",

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T1 - OGA inhibition by GlcNAc-selenazoline

AU - Kim, Eun Ju

AU - Love, Dona C.

AU - Darout, Etzer

AU - Abdo, Mohannad

AU - Rempel, Brian

AU - Withers, Stephen G.

AU - Rablen, Paul R.

AU - Hanover, John A.

AU - Knapp, Spencer

N1 - Funding Information: We are grateful to NIH ( SK, AI055760 ) and the Henry Dreyfus Teacher-Scholar Awards Program (P.R.R.) for partial financial support, UNCF-Merck for a graduate fellowship to E.D., the Canadian Institutes for Health Research and the Natural Science and Engineering Research Council (S.G.W. and B.R.), the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH (J.A.H.), and the National Research Foundation of Korea ( EJK, 20090065 ).

PY - 2010/10/1

Y1 - 2010/10/1

N2 - The title compound, which differs from the powerful O-GlcNAcase (OGA) inhibitor GlcNAc-thiazoline only at the chalcogen atom (Se for S), is a much weaker inhibitor in a direct OGA assay. In human cells, however, the selenazoline shows comparable ability to induce hyper-O-GlcNAc-ylation, and the two show similar reduction of insulin-stimulated translocation of glucose transporter 4 in differentiated 3T3 adipocytes.

AB - The title compound, which differs from the powerful O-GlcNAcase (OGA) inhibitor GlcNAc-thiazoline only at the chalcogen atom (Se for S), is a much weaker inhibitor in a direct OGA assay. In human cells, however, the selenazoline shows comparable ability to induce hyper-O-GlcNAc-ylation, and the two show similar reduction of insulin-stimulated translocation of glucose transporter 4 in differentiated 3T3 adipocytes.

KW - Hyperglycemia

KW - Lipophilicity

KW - N-Acetylhexosaminidase

KW - Post-translational modification

KW - Transcription factor

KW - Transition state

KW - Woollins reagent

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AN - SCOPUS:77956652715

SN - 0968-0896

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EP - 7064

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 19

ER -

OGA inhibition by GlcNAc-selenazoline

Abstract

All Science Journal Classification (ASJC) codes

Keywords

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