Thiodisaccharide Sulfoxides: Absolute Configuration of the SO Sulfur Atom and Influence on the Biological Activity towards the β-Galactosidase from E. coli

Benzyl 3-deoxy-4-S-(β-D-galactopyranosyl)-4-thio-β-D-threo-pentopyranoside (3) is a potent inhibitor of the β-galactosidase from Escherichia coli synthesized in our laboratory. The 2',3',4',6'-tetra-O-acetyl derivative of this thiodisaccharide was oxidized with m-chloroperoxybenz...

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Autor principal: Varela, Oscar José
Publicado: 2015
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Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_1434193X_v_n_p_Colomer
http://hdl.handle.net/20.500.12110/paper_1434193X_v_n_p_Colomer
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spelling paper:paper_1434193X_v_n_p_Colomer2023-06-08T16:14:26Z Thiodisaccharide Sulfoxides: Absolute Configuration of the SO Sulfur Atom and Influence on the Biological Activity towards the β-Galactosidase from E. coli Varela, Oscar José Biomimetics Carbohydrates Configuration determination Enzymes Inhibitors Sulfoxides Benzyl 3-deoxy-4-S-(β-D-galactopyranosyl)-4-thio-β-D-threo-pentopyranoside (3) is a potent inhibitor of the β-galactosidase from Escherichia coli synthesized in our laboratory. The 2',3',4',6'-tetra-O-acetyl derivative of this thiodisaccharide was oxidized with m-chloroperoxybenzoic acid to give a 2:1 diastereomeric mixture of sulfoxides 2S and 2R. The absolute configurations of their sulfur stereocenters were determined by using NMR techniques and by taking into account the anisotropic effects of the S=O group in the major conformers. O-Deacetylation of 2S and 2R afforded the free thiodisaccharide S-oxides 4S and 4R, which were evaluated as inhibitors of the above-mentioned enzyme. The kinetic studies showed that 4S and 4R are competitive inhibitors of the enzyme with Ki values of 0.19 and 0.45 mM, respectively. Further enzymatic reactions demonstrated that 4S is also a substrate of the β-galactosidase, as it was diastereoselectively hydrolyzed, with 4R remaining unchanged under the same conditions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Fil:Varela, O. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2015 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_1434193X_v_n_p_Colomer http://hdl.handle.net/20.500.12110/paper_1434193X_v_n_p_Colomer
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic Biomimetics
Carbohydrates
Configuration determination
Enzymes
Inhibitors
Sulfoxides
spellingShingle Biomimetics
Carbohydrates
Configuration determination
Enzymes
Inhibitors
Sulfoxides
Varela, Oscar José
Thiodisaccharide Sulfoxides: Absolute Configuration of the SO Sulfur Atom and Influence on the Biological Activity towards the β-Galactosidase from E. coli
topic_facet Biomimetics
Carbohydrates
Configuration determination
Enzymes
Inhibitors
Sulfoxides
description Benzyl 3-deoxy-4-S-(β-D-galactopyranosyl)-4-thio-β-D-threo-pentopyranoside (3) is a potent inhibitor of the β-galactosidase from Escherichia coli synthesized in our laboratory. The 2',3',4',6'-tetra-O-acetyl derivative of this thiodisaccharide was oxidized with m-chloroperoxybenzoic acid to give a 2:1 diastereomeric mixture of sulfoxides 2S and 2R. The absolute configurations of their sulfur stereocenters were determined by using NMR techniques and by taking into account the anisotropic effects of the S=O group in the major conformers. O-Deacetylation of 2S and 2R afforded the free thiodisaccharide S-oxides 4S and 4R, which were evaluated as inhibitors of the above-mentioned enzyme. The kinetic studies showed that 4S and 4R are competitive inhibitors of the enzyme with Ki values of 0.19 and 0.45 mM, respectively. Further enzymatic reactions demonstrated that 4S is also a substrate of the β-galactosidase, as it was diastereoselectively hydrolyzed, with 4R remaining unchanged under the same conditions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
author Varela, Oscar José
author_facet Varela, Oscar José
author_sort Varela, Oscar José
title Thiodisaccharide Sulfoxides: Absolute Configuration of the SO Sulfur Atom and Influence on the Biological Activity towards the β-Galactosidase from E. coli
title_short Thiodisaccharide Sulfoxides: Absolute Configuration of the SO Sulfur Atom and Influence on the Biological Activity towards the β-Galactosidase from E. coli
title_full Thiodisaccharide Sulfoxides: Absolute Configuration of the SO Sulfur Atom and Influence on the Biological Activity towards the β-Galactosidase from E. coli
title_fullStr Thiodisaccharide Sulfoxides: Absolute Configuration of the SO Sulfur Atom and Influence on the Biological Activity towards the β-Galactosidase from E. coli
title_full_unstemmed Thiodisaccharide Sulfoxides: Absolute Configuration of the SO Sulfur Atom and Influence on the Biological Activity towards the β-Galactosidase from E. coli
title_sort thiodisaccharide sulfoxides: absolute configuration of the so sulfur atom and influence on the biological activity towards the β-galactosidase from e. coli
publishDate 2015
url https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_1434193X_v_n_p_Colomer
http://hdl.handle.net/20.500.12110/paper_1434193X_v_n_p_Colomer
work_keys_str_mv AT varelaoscarjose thiodisaccharidesulfoxidesabsoluteconfigurationofthesosulfuratomandinfluenceonthebiologicalactivitytowardsthebgalactosidasefromecoli
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