Synthesis of galactofuranosyl-(1 → 5)-thiodisaccharide glycomimetics as inhibitors of a β-D-galactofuranosidase

Autores
Lo Fiego, Marcos Jacinto; Marino, María Carla; Varela, Oscar Jose
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The first synthesis of methyl β-D-galactofuranosyl-(1 → 5)-thiofuranosides is reported. These molecules, which have the 6-deoxy-5-thio derivative of L-altrofuranose (16) or D-galactofuranose (18) as the reducing end, are mimetics of the motif β-D-Galf-(1 → 5)-D-Galf found in glycoconjugates of many pathogenic microorganisms. The conformational preferences of 16 and 18 in solution were assessed by means of molecular modeling and NMR techniques. These thiodisaccharides have been evaluated as inhibitors of the β-D-galactofuranosidase from Penicillium fellutanum. The kinetics of the inhibition showed that they behave as competitive inhibitors. As expected, compound 18 (Ki = 0.15 mM), with the same configuration for the reducing end as the natural substrate of the enzyme, was a stronger inhibitor than 16 (Ki = 2.23 mM).
Fil: Lo Fiego, Marcos Jacinto. 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: Marino, María Carla. 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: 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
Thiogalactofuranosyl Disaccharide
5-Thiogalactofuranose
Exo-B-D-Galactofuranoside
Enzyme Inhibition
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/17725
Acceder
id CONICETDig_b23fdc9428bf0ddfca89da1460c33fc7
oai_identifier_str oai:ri.conicet.gov.ar:11336/17725
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Synthesis of galactofuranosyl-(1 → 5)-thiodisaccharide glycomimetics as inhibitors of a β-D-galactofuranosidaseLo Fiego, Marcos JacintoMarino, María CarlaVarela, Oscar JoseThiogalactofuranosyl Disaccharide5-ThiogalactofuranoseExo-B-D-GalactofuranosideEnzyme Inhibitionhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1The first synthesis of methyl β-D-galactofuranosyl-(1 → 5)-thiofuranosides is reported. These molecules, which have the 6-deoxy-5-thio derivative of L-altrofuranose (16) or D-galactofuranose (18) as the reducing end, are mimetics of the motif β-D-Galf-(1 → 5)-D-Galf found in glycoconjugates of many pathogenic microorganisms. The conformational preferences of 16 and 18 in solution were assessed by means of molecular modeling and NMR techniques. These thiodisaccharides have been evaluated as inhibitors of the β-D-galactofuranosidase from Penicillium fellutanum. The kinetics of the inhibition showed that they behave as competitive inhibitors. As expected, compound 18 (Ki = 0.15 mM), with the same configuration for the reducing end as the natural substrate of the enzyme, was a stronger inhibitor than 16 (Ki = 2.23 mM).Fil: Lo Fiego, Marcos Jacinto. 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: Marino, María Carla. 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: 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; ArgentinaRoyal Society of Chemistry2015-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/17725Lo Fiego, Marcos Jacinto; Marino, María Carla; Varela, Oscar Jose; Synthesis of galactofuranosyl-(1 → 5)-thiodisaccharide glycomimetics as inhibitors of a β-D-galactofuranosidase; Royal Society of Chemistry; RSC Advances; 5; 5-2015; 45631-456402046-2069enginfo:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/10.1039/c5ra06899ainfo:eu-repo/semantics/altIdentifier/url/https://pubs.rsc.org/en/content/articlelanding/2015/RA/C5RA06899Ainfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T10:42:17Zoai:ri.conicet.gov.ar:11336/17725instacron: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:34982025-09-17 10:42:18.009CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Synthesis of galactofuranosyl-(1 → 5)-thiodisaccharide glycomimetics as inhibitors of a β-D-galactofuranosidase
title Synthesis of galactofuranosyl-(1 → 5)-thiodisaccharide glycomimetics as inhibitors of a β-D-galactofuranosidase
spellingShingle Synthesis of galactofuranosyl-(1 → 5)-thiodisaccharide glycomimetics as inhibitors of a β-D-galactofuranosidase
Lo Fiego, Marcos Jacinto
Thiogalactofuranosyl Disaccharide
5-Thiogalactofuranose
Exo-B-D-Galactofuranoside
Enzyme Inhibition
title_short Synthesis of galactofuranosyl-(1 → 5)-thiodisaccharide glycomimetics as inhibitors of a β-D-galactofuranosidase
title_full Synthesis of galactofuranosyl-(1 → 5)-thiodisaccharide glycomimetics as inhibitors of a β-D-galactofuranosidase
title_fullStr Synthesis of galactofuranosyl-(1 → 5)-thiodisaccharide glycomimetics as inhibitors of a β-D-galactofuranosidase
title_full_unstemmed Synthesis of galactofuranosyl-(1 → 5)-thiodisaccharide glycomimetics as inhibitors of a β-D-galactofuranosidase
title_sort Synthesis of galactofuranosyl-(1 → 5)-thiodisaccharide glycomimetics as inhibitors of a β-D-galactofuranosidase
dc.creator.none.fl_str_mv Lo Fiego, Marcos Jacinto
Marino, María Carla
Varela, Oscar Jose
author Lo Fiego, Marcos Jacinto
author_facet Lo Fiego, Marcos Jacinto
Marino, María Carla
Varela, Oscar Jose
author_role author
author2 Marino, María Carla
Varela, Oscar Jose
author2_role author
author
dc.subject.none.fl_str_mv Thiogalactofuranosyl Disaccharide
5-Thiogalactofuranose
Exo-B-D-Galactofuranoside
Enzyme Inhibition
topic Thiogalactofuranosyl Disaccharide
5-Thiogalactofuranose
Exo-B-D-Galactofuranoside
Enzyme Inhibition
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The first synthesis of methyl β-D-galactofuranosyl-(1 → 5)-thiofuranosides is reported. These molecules, which have the 6-deoxy-5-thio derivative of L-altrofuranose (16) or D-galactofuranose (18) as the reducing end, are mimetics of the motif β-D-Galf-(1 → 5)-D-Galf found in glycoconjugates of many pathogenic microorganisms. The conformational preferences of 16 and 18 in solution were assessed by means of molecular modeling and NMR techniques. These thiodisaccharides have been evaluated as inhibitors of the β-D-galactofuranosidase from Penicillium fellutanum. The kinetics of the inhibition showed that they behave as competitive inhibitors. As expected, compound 18 (Ki = 0.15 mM), with the same configuration for the reducing end as the natural substrate of the enzyme, was a stronger inhibitor than 16 (Ki = 2.23 mM).
Fil: Lo Fiego, Marcos Jacinto. 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: Marino, María Carla. 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: 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 The first synthesis of methyl β-D-galactofuranosyl-(1 → 5)-thiofuranosides is reported. These molecules, which have the 6-deoxy-5-thio derivative of L-altrofuranose (16) or D-galactofuranose (18) as the reducing end, are mimetics of the motif β-D-Galf-(1 → 5)-D-Galf found in glycoconjugates of many pathogenic microorganisms. The conformational preferences of 16 and 18 in solution were assessed by means of molecular modeling and NMR techniques. These thiodisaccharides have been evaluated as inhibitors of the β-D-galactofuranosidase from Penicillium fellutanum. The kinetics of the inhibition showed that they behave as competitive inhibitors. As expected, compound 18 (Ki = 0.15 mM), with the same configuration for the reducing end as the natural substrate of the enzyme, was a stronger inhibitor than 16 (Ki = 2.23 mM).
publishDate 2015
dc.date.none.fl_str_mv 2015-05
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/11336/17725
Lo Fiego, Marcos Jacinto; Marino, María Carla; Varela, Oscar Jose; Synthesis of galactofuranosyl-(1 → 5)-thiodisaccharide glycomimetics as inhibitors of a β-D-galactofuranosidase; Royal Society of Chemistry; RSC Advances; 5; 5-2015; 45631-45640
2046-2069
url http://hdl.handle.net/11336/17725
identifier_str_mv Lo Fiego, Marcos Jacinto; Marino, María Carla; Varela, Oscar Jose; Synthesis of galactofuranosyl-(1 → 5)-thiodisaccharide glycomimetics as inhibitors of a β-D-galactofuranosidase; Royal Society of Chemistry; RSC Advances; 5; 5-2015; 45631-45640
2046-2069
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/10.1039/c5ra06899a
info:eu-repo/semantics/altIdentifier/url/https://pubs.rsc.org/en/content/articlelanding/2015/RA/C5RA06899A
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc/2.5/ar/
dc.format.none.fl_str_mv application/pdf
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
_version_ 1843605890209415168
score 13.001348

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