Abstract
Anionic O2 derivatives of methyl 3-deoxy-3-(4-methylbenzamido)-1-thio-beta-D-galactopyranoside have been synthesized as inhibitors against galectin-3. The sulfate, H-phosphonate, and benzyl phosphate derivatives showed an increased affinity as compared to the parent unsubstituted galactopyranoside. Modeling revealed arginine-144 being pinched by the C3 benzamide and O2 anionic substituents in that the benzamide stacked face-to-face and the anionic O2 substituent ion-paired with the guanidinium moiety.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Arginine* / analogs & derivatives
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Arginine* / chemical synthesis
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Arginine* / pharmacology
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Benzamides / chemical synthesis*
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Benzamides / chemistry
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Benzamides / pharmacology*
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Binding Sites
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Binding, Competitive
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Drug Design
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Galactose / chemistry*
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Galactosides / chemical synthesis*
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Galactosides / chemistry
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Galactosides / pharmacology*
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Galectin 3 / antagonists & inhibitors*
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Models, Molecular
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Molecular Conformation
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Oxygen / chemistry
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Benzamides
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Galactosides
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Galectin 3
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Arginine
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Oxygen
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Galactose