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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/50484
Ver los metadatos del registro completo
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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 Técnicas2025-09-03T10:02:58Zoai: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:34982025-09-03 10:02:58.818CONICET 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 |
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1842269777084547072 |
score |
13.13397 |