Glycosidase inhibition by ring-modified castanospermine analogues: tackling enzyme selectivity by inhibitor tailoring

Matilde Aguilar-Moncayo; Tracey M. Gloster; Johan P. Turkenburg; M. Isabel Garcia-Moreno; Carmen Ortiz Mellet; Gideon J. Davies; Jose M. Garcia Fernandez

doi:10.1039/b906968b

Glycosidase inhibition by ring-modified castanospermine analogues: tackling enzyme selectivity by inhibitor tailoring

Matilde Aguilar-Moncayo, Tracey M. Gloster, Johan P. Turkenburg, M. Isabel Garcia-Moreno, Carmen Ortiz Mellet, Gideon J. Davies, Jose M. Garcia Fernandez

Chemistry

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

Abstract

Synthesis of a panel of iso(thio)urea-type ring-modified castanospermine analogues bearing a freely mutarotating pseudoanomeric hydroxyl group results in tight-binding beta-glucosidase inhibitors with unusual binding signatures; the presence of an N-octyl substituent imparts a remarkable anomeric selectivity, promoting strong binding of the appropriate beta-anomer by the beta-glucosidase.

Original language	English
Pages (from-to)	2738-2747
Number of pages	10
Journal	Organic and Biomolecular Chemistry
Volume	7
Issue number	13
DOIs	https://doi.org/10.1039/b906968b
Publication status	Published - 2009

Keywords

BETA-GLUCOSIDASE
TRANSITION-STATE
BIOLOGICAL EVALUATION
GLYCOGEN-PHOSPHORYLASE
CYCLODEXTRIN ANALOGS
MOLECULAR-BASIS
HIGHLY POTENT
BINDING
GLYCOMIMETICS
ISOFAGOMINE

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title = "Glycosidase inhibition by ring-modified castanospermine analogues: tackling enzyme selectivity by inhibitor tailoring",

abstract = "Synthesis of a panel of iso(thio)urea-type ring-modified castanospermine analogues bearing a freely mutarotating pseudoanomeric hydroxyl group results in tight-binding beta-glucosidase inhibitors with unusual binding signatures; the presence of an N-octyl substituent imparts a remarkable anomeric selectivity, promoting strong binding of the appropriate beta-anomer by the beta-glucosidase.",

keywords = "BETA-GLUCOSIDASE, TRANSITION-STATE, BIOLOGICAL EVALUATION, GLYCOGEN-PHOSPHORYLASE, CYCLODEXTRIN ANALOGS, MOLECULAR-BASIS, HIGHLY POTENT, BINDING, GLYCOMIMETICS, ISOFAGOMINE",

author = "Matilde Aguilar-Moncayo and Gloster, {Tracey M.} and Turkenburg, {Johan P.} and {Isabel Garcia-Moreno}, M. and {Ortiz Mellet}, Carmen and Davies, {Gideon J.} and {Garcia Fernandez}, {Jose M.}",

year = "2009",

doi = "10.1039/b906968b",

language = "English",

volume = "7",

pages = "2738--2747",

journal = "Organic and Biomolecular Chemistry",

issn = "1477-0520",

publisher = "The Royal Society of Chemistry",

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T1 - Glycosidase inhibition by ring-modified castanospermine analogues: tackling enzyme selectivity by inhibitor tailoring

AU - Aguilar-Moncayo, Matilde

AU - Gloster, Tracey M.

AU - Turkenburg, Johan P.

AU - Isabel Garcia-Moreno, M.

AU - Ortiz Mellet, Carmen

AU - Davies, Gideon J.

AU - Garcia Fernandez, Jose M.

PY - 2009

Y1 - 2009

N2 - Synthesis of a panel of iso(thio)urea-type ring-modified castanospermine analogues bearing a freely mutarotating pseudoanomeric hydroxyl group results in tight-binding beta-glucosidase inhibitors with unusual binding signatures; the presence of an N-octyl substituent imparts a remarkable anomeric selectivity, promoting strong binding of the appropriate beta-anomer by the beta-glucosidase.

AB - Synthesis of a panel of iso(thio)urea-type ring-modified castanospermine analogues bearing a freely mutarotating pseudoanomeric hydroxyl group results in tight-binding beta-glucosidase inhibitors with unusual binding signatures; the presence of an N-octyl substituent imparts a remarkable anomeric selectivity, promoting strong binding of the appropriate beta-anomer by the beta-glucosidase.

KW - BETA-GLUCOSIDASE

KW - TRANSITION-STATE

KW - BIOLOGICAL EVALUATION

KW - GLYCOGEN-PHOSPHORYLASE

KW - CYCLODEXTRIN ANALOGS

KW - MOLECULAR-BASIS

KW - HIGHLY POTENT

KW - BINDING

KW - GLYCOMIMETICS

KW - ISOFAGOMINE

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U2 - 10.1039/b906968b

DO - 10.1039/b906968b

M3 - Article

SN - 1477-0520

VL - 7

SP - 2738

EP - 2747

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

IS - 13

ER -

Glycosidase inhibition by ring-modified castanospermine analogues: tackling enzyme selectivity by inhibitor tailoring

Abstract

Keywords

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