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Abstract:

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.

Registro:

Documento: Artículo
Título:Thiodisaccharide Sulfoxides: Absolute Configuration of the SO Sulfur Atom and Influence on the Biological Activity towards the β-Galactosidase from E. coli
Autor:Colomer, J.P.; Canales Mayordomo, M.A.; Fernández de Toro, B.; Jiménez-Barbero, J.; Varela, O.
Filiación:CIHIDECAR-CONICET-UBA, Depto. Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires Ciudad Universitaria, Pab. II, 1428 Buenos Aires, Argentina
Depto. Química Orgánica I, Facultad Ciencias Químicas, Universidad Complutense de Madrid, Avd. Complutense s/n, 28040 Madrid, Spain
Department of Chemical and Physical Biology, Centro de Investigaciones Biológicas, CSIC, Ramiro Maeztu 9, 28040 Madrid, Spain
Structural Biology Unit, CIC bioGUNE, Parque Tecnológico de Bizkaia Building 801A, 48160 Derio, Spain
IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain
Palabras clave:Biomimetics; Carbohydrates; Configuration determination; Enzymes; Inhibitors; Sulfoxides
Año:2015
DOI: http://dx.doi.org/10.1002/ejoc.201403609
Título revista:European Journal of Organic Chemistry
Título revista abreviado:Eur. J. Org. Chem.
ISSN:1434193X
CODEN:EJOCF
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_1434193X_v_n_p_Colomer

Citas:

---------- APA ----------
Colomer, J.P., Canales Mayordomo, M.A., Fernández de Toro, B., Jiménez-Barbero, J. & Varela, O. (2015) . Thiodisaccharide Sulfoxides: Absolute Configuration of the SO Sulfur Atom and Influence on the Biological Activity towards the β-Galactosidase from E. coli. European Journal of Organic Chemistry.
http://dx.doi.org/10.1002/ejoc.201403609
---------- CHICAGO ----------
Colomer, J.P., Canales Mayordomo, M.A., Fernández de Toro, B., Jiménez-Barbero, J., Varela, O. "Thiodisaccharide Sulfoxides: Absolute Configuration of the SO Sulfur Atom and Influence on the Biological Activity towards the β-Galactosidase from E. coli" . European Journal of Organic Chemistry (2015).
http://dx.doi.org/10.1002/ejoc.201403609
---------- MLA ----------
Colomer, J.P., Canales Mayordomo, M.A., Fernández de Toro, B., Jiménez-Barbero, J., Varela, O. "Thiodisaccharide Sulfoxides: Absolute Configuration of the SO Sulfur Atom and Influence on the Biological Activity towards the β-Galactosidase from E. coli" . European Journal of Organic Chemistry, 2015.
http://dx.doi.org/10.1002/ejoc.201403609
---------- VANCOUVER ----------
Colomer, J.P., Canales Mayordomo, M.A., Fernández de Toro, B., Jiménez-Barbero, J., Varela, O. Thiodisaccharide Sulfoxides: Absolute Configuration of the SO Sulfur Atom and Influence on the Biological Activity towards the β-Galactosidase from E. coli. Eur. J. Org. Chem. 2015.
http://dx.doi.org/10.1002/ejoc.201403609