N-Acetylhexosaminidase inhibitory properties of C-1 homologated GlcNAc- and GalNAc-thiazolines

Benjamin Amorelli; Chunhua Yang; Brian Rempel; Stephen G. Withers; Spencer Knapp

doi:10.1016/j.bmcl.2008.03.067

N-Acetylhexosaminidase inhibitory properties of C-1 homologated GlcNAc- and GalNAc-thiazolines

Benjamin Amorelli, Chunhua Yang, Brian Rempel, Stephen G. Withers, Spencer Knapp

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

20 Scopus citations

Abstract

Several C-1 homologated GlcNAc- and GalNAc-thiazolines, as well as a related GalNAc-thiazole, have been prepared. The compounds are analogues of GlcNAc-thiazoline, a potent transition-state-mimicking inhibitor of retaining β-N-acetylglycosaminidases. Kinetic evaluation of these fused pyranose-heterocycles against the bacterial N-acetylhexosaminidase SpHex suggests active site steric restrictions around the substrate anomeric carbon.

Original language	English (US)
Pages (from-to)	2944-2947
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	9
DOIs	https://doi.org/10.1016/j.bmcl.2008.03.067
State	Published - May 1 2008

All Science Journal Classification (ASJC) codes

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

Keywords

Glycosidase
O-GlcNAcase
Pyranose conformation
Streptomyces plicatus
Transition state mimic

Access to Document

10.1016/j.bmcl.2008.03.067

Cite this

@article{f4c4b4ce199e43e2819c11d95713b0c0,

title = "N-Acetylhexosaminidase inhibitory properties of C-1 homologated GlcNAc- and GalNAc-thiazolines",

abstract = "Several C-1 homologated GlcNAc- and GalNAc-thiazolines, as well as a related GalNAc-thiazole, have been prepared. The compounds are analogues of GlcNAc-thiazoline, a potent transition-state-mimicking inhibitor of retaining β-N-acetylglycosaminidases. Kinetic evaluation of these fused pyranose-heterocycles against the bacterial N-acetylhexosaminidase SpHex suggests active site steric restrictions around the substrate anomeric carbon.",

keywords = "Glycosidase, O-GlcNAcase, Pyranose conformation, Streptomyces plicatus, Transition state mimic",

author = "Benjamin Amorelli and Chunhua Yang and Brian Rempel and Withers, {Stephen G.} and Spencer Knapp",

note = "Funding Information: We thank NIH (AI055760) for partial financial support, and Rutgers University for a Reid graduate fellowship to B.A. The work at UBC was supported by the Canadian Institutes for Health Research, the Natural Science and Engineering Research Council, and the University of British Columbia. We thank Dr. Brian Patrick and David Vocadlo at UBC for determining the 3-dimensional structure of 1b . ",

year = "2008",

month = may,

day = "1",

doi = "10.1016/j.bmcl.2008.03.067",

language = "English (US)",

volume = "18",

pages = "2944--2947",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "9",

}

TY - JOUR

T1 - N-Acetylhexosaminidase inhibitory properties of C-1 homologated GlcNAc- and GalNAc-thiazolines

AU - Amorelli, Benjamin

AU - Yang, Chunhua

AU - Rempel, Brian

AU - Withers, Stephen G.

AU - Knapp, Spencer

N1 - Funding Information: We thank NIH (AI055760) for partial financial support, and Rutgers University for a Reid graduate fellowship to B.A. The work at UBC was supported by the Canadian Institutes for Health Research, the Natural Science and Engineering Research Council, and the University of British Columbia. We thank Dr. Brian Patrick and David Vocadlo at UBC for determining the 3-dimensional structure of 1b .

PY - 2008/5/1

Y1 - 2008/5/1

N2 - Several C-1 homologated GlcNAc- and GalNAc-thiazolines, as well as a related GalNAc-thiazole, have been prepared. The compounds are analogues of GlcNAc-thiazoline, a potent transition-state-mimicking inhibitor of retaining β-N-acetylglycosaminidases. Kinetic evaluation of these fused pyranose-heterocycles against the bacterial N-acetylhexosaminidase SpHex suggests active site steric restrictions around the substrate anomeric carbon.

AB - Several C-1 homologated GlcNAc- and GalNAc-thiazolines, as well as a related GalNAc-thiazole, have been prepared. The compounds are analogues of GlcNAc-thiazoline, a potent transition-state-mimicking inhibitor of retaining β-N-acetylglycosaminidases. Kinetic evaluation of these fused pyranose-heterocycles against the bacterial N-acetylhexosaminidase SpHex suggests active site steric restrictions around the substrate anomeric carbon.

KW - Glycosidase

KW - O-GlcNAcase

KW - Pyranose conformation

KW - Streptomyces plicatus

KW - Transition state mimic

UR - http://www.scopus.com/inward/record.url?scp=42949095576&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42949095576&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2008.03.067

DO - 10.1016/j.bmcl.2008.03.067

M3 - Article

C2 - 18406613

AN - SCOPUS:42949095576

SN - 0960-894X

VL - 18

SP - 2944

EP - 2947

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 9

ER -

N-Acetylhexosaminidase inhibitory properties of C-1 homologated GlcNAc- and GalNAc-thiazolines

Abstract

All Science Journal Classification (ASJC) codes

Keywords

Access to Document

Other files and links

Fingerprint

Cite this