Synthesis and biological activity of divalent ligands based on 3-deoxy-4-thiolactose, an isosteric analogue of lactose

Autores
Cagnoni, Alejandro; Varela, Oscar Jose; Kovensky, José Eduardo; Uhrig, Maria Laura
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We report here the synthesis of divalent ligands containing 3-deoxy-4-thiolactose. This thiodisaccharide has been synthesized using the Michael addition of β-1-thiogalactose to the α,β-unsaturated system of sugar-derived dihydropyranones, followed by the reduction of the remaining carbonyl group. We were able to control the configuration (S) of the stereocenter linked to sulfur (C-4) of the reducing end by conducting the thioglycosylation at high temperature or by isomerization during the reduction of the 2-ulose thiodisaccharide with NaBH4/THF. The energy profile for this reaction on a model compound was calculated. The anomeric position of the 3-deoxy-4-thiolactose was functionalized with a terminal alkyne, which was coupled to azide-containing sugar scaffolds through CuAAC reaction to afford mono- and divalent ligands. The final products were competitive inhibitors of E. coli β-galactosidase in the micromolar range. Their binding affinities to peanut agglutinin (PNA) were determined by isothermal calorimetry, which showed a clear decrease in the Ka values for monovalent derivatives compared to lactose. This report contributes to establishing the role of a particular hydroxyl group of lactose in sugarprotein recognition processes.
Fil: Cagnoni, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono; Argentina
Fil: Varela, Oscar Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono; Argentina
Fil: Kovensky, José Eduardo. No especifíca;
Fil: Uhrig, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono; Argentina
Materia
Multivalent Ligands
Michael Addition
Glycosidase Inhibition
Lectin Affinity
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:11336/2136
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/2136
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Synthesis and biological activity of divalent ligands based on 3-deoxy-4-thiolactose, an isosteric analogue of lactoseCagnoni, AlejandroVarela, Oscar JoseKovensky, José EduardoUhrig, Maria LauraMultivalent LigandsMichael AdditionGlycosidase InhibitionLectin Affinityhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1We report here the synthesis of divalent ligands containing 3-deoxy-4-thiolactose. This thiodisaccharide has been synthesized using the Michael addition of β-1-thiogalactose to the α,β-unsaturated system of sugar-derived dihydropyranones, followed by the reduction of the remaining carbonyl group. We were able to control the configuration (S) of the stereocenter linked to sulfur (C-4) of the reducing end by conducting the thioglycosylation at high temperature or by isomerization during the reduction of the 2-ulose thiodisaccharide with NaBH4/THF. The energy profile for this reaction on a model compound was calculated. The anomeric position of the 3-deoxy-4-thiolactose was functionalized with a terminal alkyne, which was coupled to azide-containing sugar scaffolds through CuAAC reaction to afford mono- and divalent ligands. The final products were competitive inhibitors of E. coli β-galactosidase in the micromolar range. Their binding affinities to peanut agglutinin (PNA) were determined by isothermal calorimetry, which showed a clear decrease in the Ka values for monovalent derivatives compared to lactose. This report contributes to establishing the role of a particular hydroxyl group of lactose in sugarprotein recognition processes.Fil: Cagnoni, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono; ArgentinaFil: Varela, Oscar Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono; ArgentinaFil: Kovensky, José Eduardo. No especifíca;Fil: Uhrig, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono; ArgentinaRoyal Society of Chemistry2013-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/2136Cagnoni, Alejandro; Varela, Oscar Jose; Kovensky, José Eduardo; Uhrig, Maria Laura; Synthesis and biological activity of divalent ligands based on 3-deoxy-4-thiolactose, an isosteric analogue of lactose; Royal Society of Chemistry; Organic & Biomolecular Chemistry; 11; 33; 7-2013; 5500-55111477-0520enginfo:eu-repo/semantics/altIdentifier/url/http://pubs.rsc.org/en/Content/ArticleLanding/OB/2013/C3OB41074A#!divAbstractinfo:eu-repo/semantics/altIdentifier/doi/DOI:10.1039/C3OB41074Ainfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:32:34Zoai:ri.conicet.gov.ar:11336/2136instacron: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 09:32:34.368CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Synthesis and biological activity of divalent ligands based on 3-deoxy-4-thiolactose, an isosteric analogue of lactose
title Synthesis and biological activity of divalent ligands based on 3-deoxy-4-thiolactose, an isosteric analogue of lactose
spellingShingle Synthesis and biological activity of divalent ligands based on 3-deoxy-4-thiolactose, an isosteric analogue of lactose
Cagnoni, Alejandro
Multivalent Ligands
Michael Addition
Glycosidase Inhibition
Lectin Affinity
title_short Synthesis and biological activity of divalent ligands based on 3-deoxy-4-thiolactose, an isosteric analogue of lactose
title_full Synthesis and biological activity of divalent ligands based on 3-deoxy-4-thiolactose, an isosteric analogue of lactose
title_fullStr Synthesis and biological activity of divalent ligands based on 3-deoxy-4-thiolactose, an isosteric analogue of lactose
title_full_unstemmed Synthesis and biological activity of divalent ligands based on 3-deoxy-4-thiolactose, an isosteric analogue of lactose
title_sort Synthesis and biological activity of divalent ligands based on 3-deoxy-4-thiolactose, an isosteric analogue of lactose
dc.creator.none.fl_str_mv Cagnoni, Alejandro
Varela, Oscar Jose
Kovensky, José Eduardo
Uhrig, Maria Laura
author Cagnoni, Alejandro
author_facet Cagnoni, Alejandro
Varela, Oscar Jose
Kovensky, José Eduardo
Uhrig, Maria Laura
author_role author
author2 Varela, Oscar Jose
Kovensky, José Eduardo
Uhrig, Maria Laura
author2_role author
author
author
dc.subject.none.fl_str_mv Multivalent Ligands
Michael Addition
Glycosidase Inhibition
Lectin Affinity
topic Multivalent Ligands
Michael Addition
Glycosidase Inhibition
Lectin Affinity
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv We report here the synthesis of divalent ligands containing 3-deoxy-4-thiolactose. This thiodisaccharide has been synthesized using the Michael addition of β-1-thiogalactose to the α,β-unsaturated system of sugar-derived dihydropyranones, followed by the reduction of the remaining carbonyl group. We were able to control the configuration (S) of the stereocenter linked to sulfur (C-4) of the reducing end by conducting the thioglycosylation at high temperature or by isomerization during the reduction of the 2-ulose thiodisaccharide with NaBH4/THF. The energy profile for this reaction on a model compound was calculated. The anomeric position of the 3-deoxy-4-thiolactose was functionalized with a terminal alkyne, which was coupled to azide-containing sugar scaffolds through CuAAC reaction to afford mono- and divalent ligands. The final products were competitive inhibitors of E. coli β-galactosidase in the micromolar range. Their binding affinities to peanut agglutinin (PNA) were determined by isothermal calorimetry, which showed a clear decrease in the Ka values for monovalent derivatives compared to lactose. This report contributes to establishing the role of a particular hydroxyl group of lactose in sugarprotein recognition processes.
Fil: Cagnoni, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono; Argentina
Fil: Varela, Oscar Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono; Argentina
Fil: Kovensky, José Eduardo. No especifíca;
Fil: Uhrig, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono; Argentina
description We report here the synthesis of divalent ligands containing 3-deoxy-4-thiolactose. This thiodisaccharide has been synthesized using the Michael addition of β-1-thiogalactose to the α,β-unsaturated system of sugar-derived dihydropyranones, followed by the reduction of the remaining carbonyl group. We were able to control the configuration (S) of the stereocenter linked to sulfur (C-4) of the reducing end by conducting the thioglycosylation at high temperature or by isomerization during the reduction of the 2-ulose thiodisaccharide with NaBH4/THF. The energy profile for this reaction on a model compound was calculated. The anomeric position of the 3-deoxy-4-thiolactose was functionalized with a terminal alkyne, which was coupled to azide-containing sugar scaffolds through CuAAC reaction to afford mono- and divalent ligands. The final products were competitive inhibitors of E. coli β-galactosidase in the micromolar range. Their binding affinities to peanut agglutinin (PNA) were determined by isothermal calorimetry, which showed a clear decrease in the Ka values for monovalent derivatives compared to lactose. This report contributes to establishing the role of a particular hydroxyl group of lactose in sugarprotein recognition processes.
publishDate 2013
dc.date.none.fl_str_mv 2013-07
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/11336/2136
Cagnoni, Alejandro; Varela, Oscar Jose; Kovensky, José Eduardo; Uhrig, Maria Laura; Synthesis and biological activity of divalent ligands based on 3-deoxy-4-thiolactose, an isosteric analogue of lactose; Royal Society of Chemistry; Organic & Biomolecular Chemistry; 11; 33; 7-2013; 5500-5511
1477-0520
url http://hdl.handle.net/11336/2136
identifier_str_mv Cagnoni, Alejandro; Varela, Oscar Jose; Kovensky, José Eduardo; Uhrig, Maria Laura; Synthesis and biological activity of divalent ligands based on 3-deoxy-4-thiolactose, an isosteric analogue of lactose; Royal Society of Chemistry; Organic & Biomolecular Chemistry; 11; 33; 7-2013; 5500-5511
1477-0520
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://pubs.rsc.org/en/Content/ArticleLanding/OB/2013/C3OB41074A#!divAbstract
info:eu-repo/semantics/altIdentifier/doi/DOI:10.1039/C3OB41074A
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 Royal Society of Chemistry
publisher.none.fl_str_mv Royal Society of Chemistry
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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score 13.070432

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