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

Autores
Colomer, Juan Pablo; Mayordomo, María Ángeles Canales; De Toro, Beatriz Fernández; Jiménez Barbero, Jesús; Varela, Oscar Jose
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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
Materia
Biomimetics
Carbohydrates
Configuration Determination
Enzymes
Inhibitors
Sulfoxides
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/50484
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/50484
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Thiodisaccharide sulfoxides: Absolute configuration of the so sulfur atom and influence on the biological activity towards the β-galactosidase from E. coliColomer, Juan PabloMayordomo, María Ángeles CanalesDe Toro, Beatriz FernándezJiménez Barbero, JesúsVarela, Oscar JoseBiomimeticsCarbohydratesConfiguration DeterminationEnzymesInhibitorsSulfoxideshttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Benzyl 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; ArgentinaFil: Mayordomo, María Ángeles Canales. Universidad Complutense de Madrid. Facultad de Ciencias Químicas; EspañaFil: De Toro, Beatriz Fernández. Consejo Superior de Investigaciones Científicas. Centro de Investigaciones Biológicas; EspañaFil: Jiménez Barbero, Jesús. Consejo Superior de Investigaciones Científicas. Centro de Investigaciones Biológicas; EspañaFil: 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; ArgentinaWiley VCH Verlag2015-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/50484Colomer, Juan Pablo; Mayordomo, María Ángeles Canales; De Toro, Beatriz Fernández; Jiménez Barbero, Jesús; Varela, Oscar Jose; Thiodisaccharide sulfoxides: Absolute configuration of the so sulfur atom and influence on the biological activity towards the β-galactosidase from E. coli; Wiley VCH Verlag; European Journal of Organic Chemistry; 2015; 7; 2-2015; 1448-14551434-193XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/ejoc.201403609info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/ejoc.201403609info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:19:19Zoai:ri.conicet.gov.ar:11336/50484instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:19:19.308CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Thiodisaccharide sulfoxides: Absolute configuration of the so sulfur atom and influence on the biological activity towards the β-galactosidase from E. coli
title Thiodisaccharide sulfoxides: Absolute configuration of the so sulfur atom and influence on the biological activity towards the β-galactosidase from E. coli
spellingShingle Thiodisaccharide sulfoxides: Absolute configuration of the so sulfur atom and influence on the biological activity towards the β-galactosidase from E. coli
Colomer, Juan Pablo
Biomimetics
Carbohydrates
Configuration Determination
Enzymes
Inhibitors
Sulfoxides
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
dc.creator.none.fl_str_mv Colomer, Juan Pablo
Mayordomo, María Ángeles Canales
De Toro, Beatriz Fernández
Jiménez Barbero, Jesús
Varela, Oscar Jose
author Colomer, Juan Pablo
author_facet Colomer, Juan Pablo
Mayordomo, María Ángeles Canales
De Toro, Beatriz Fernández
Jiménez Barbero, Jesús
Varela, Oscar Jose
author_role author
author2 Mayordomo, María Ángeles Canales
De Toro, Beatriz Fernández
Jiménez Barbero, Jesús
Varela, Oscar Jose
author2_role author
author
author
author
dc.subject.none.fl_str_mv Biomimetics
Carbohydrates
Configuration Determination
Enzymes
Inhibitors
Sulfoxides
topic Biomimetics
Carbohydrates
Configuration Determination
Enzymes
Inhibitors
Sulfoxides
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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
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.
publishDate 2015
dc.date.none.fl_str_mv 2015-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/50484
Colomer, Juan Pablo; Mayordomo, María Ángeles Canales; De Toro, Beatriz Fernández; Jiménez Barbero, Jesús; Varela, Oscar Jose; Thiodisaccharide sulfoxides: Absolute configuration of the so sulfur atom and influence on the biological activity towards the β-galactosidase from E. coli; Wiley VCH Verlag; European Journal of Organic Chemistry; 2015; 7; 2-2015; 1448-1455
1434-193X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/50484
identifier_str_mv Colomer, Juan Pablo; Mayordomo, María Ángeles Canales; De Toro, Beatriz Fernández; Jiménez Barbero, Jesús; Varela, Oscar Jose; Thiodisaccharide sulfoxides: Absolute configuration of the so sulfur atom and influence on the biological activity towards the β-galactosidase from E. coli; Wiley VCH Verlag; European Journal of Organic Chemistry; 2015; 7; 2-2015; 1448-1455
1434-193X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/ejoc.201403609
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/ejoc.201403609
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley VCH Verlag
publisher.none.fl_str_mv Wiley VCH Verlag
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1844614163962265600
score 13.070432

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