Access to Galectin‑3 Inhibitors from Chemoenzymatic Synthons

Chemoenzymatic strategies are useful for providing both regio- and stereoselective access to bioactive oligosaccharides. We show herein that a glycosynthase mutant of a Thermus thermophilus α-glycosidase can react with unnatural glycosides such as 6-azido-6-deoxy-d-glucose/glucosamine to lead to β-d...

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Published inJournal of organic chemistry Vol. 85; no. 24; pp. 16099 - 16114
Main Authors Dussouy, Christophe, Téletchéa, Stéphane, Lambert, Annie, Charlier, Cathy, Botez, Iuliana, Ceuninck, Frédéric De, Grandjean, Cyrille
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 18.12.2020
Amer Chemical Soc
Subjects
Chemistry
Chemistry, Organic
Physical Sciences
Science & Technology
MUTANT GLYCOSIDASES
CELLS
DESIGN
ARGININE-ARENE INTERACTIONS
GLYCOSYNTHASES
BINDING
DERIVATIVES
WATER
TOOLS
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Summary:Chemoenzymatic strategies are useful for providing both regio- and stereoselective access to bioactive oligosaccharides. We show herein that a glycosynthase mutant of a Thermus thermophilus α-glycosidase can react with unnatural glycosides such as 6-azido-6-deoxy-d-glucose/glucosamine to lead to β-d-galactopyranosyl-(1→3)-d-glucopyranoside or β-d-galactopyranosyl-(1→3)-2-acetamido-2-deoxy-d-glucopyranoside derivatives bearing a unique azide function. Taking advantage of the orthogonality between the azide and the hydroxyl functional groups, the former was next selectively reacted to give rise to a library of galectin-3 inhibitors. Combining enzyme substrate promiscuity and bioorthogonality thus appears as a powerful strategy to rapidly access to sugar-based ligands.
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ISSN:0022-3263
1520-6904
DOI:10.1021/acs.joc.0c01927