Thiodisaccharide sulfoxides: Absolute configuration of the so sulfur atom and influence on the biological activity towards the β-galactosidase from E. coli

Authors
Colomer, Juan Pablo; Mayordomo, María Ángeles Canales; De Toro, Beatriz Fernández; Jiménez Barbero, Jesús; Varela, Oscar Jose
Publication Year
2015
Language
English
Format
article
Status
Published version
Description
Benzyl 3-deoxy-4-S-(β-D-galactopyranosyl)-4-thio-β-D-threopentopyranoside (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.
Fil: Colomer, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina
Fil: Mayordomo, María Ángeles Canales. Universidad Complutense de Madrid. Facultad de Ciencias Químicas; España
Fil: De Toro, Beatriz Fernández. Consejo Superior de Investigaciones Científicas. Centro de Investigaciones Biológicas; España
Fil: Jiménez Barbero, Jesús. Consejo Superior de Investigaciones Científicas. Centro de Investigaciones Biológicas; España
Fil: Varela, Oscar Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina
Subject
BIOMIMETICS
CARBOHYDRATES
CONFIGURATION DETERMINATION
ENZYMES
INHIBITORS
SULFOXIDES
Otras Ciencias Químicas
Ciencias Químicas
CIENCIAS NATURALES Y EXACTAS
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/50484