Selectively Modified Lactose and N-Acetyllactosamine Analogs at Three Key Positions to Afford Effective Galectin-3 Ligands

Autores
Abdullayev, Shuay; Kadav, Priyanka; Bandyopadhyay, Purnima; Medrano, Francisco Javier; Rabinovich, Gabriel Adrián; Dam, Tarun K.; Romero, Antonio; Roy, René
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Galectins constitute a family of galactose-binding lectins overly expressed in the tumor microenvironment as well as in innate and adaptive immune cells, in inflammatory diseases. Lactose ((β-D-galactopyranosyl)-(1→4)-β-D-glucopyranose, Lac) and N-Acetyllactosamine (2-acetamido-2-deoxy-4-O-β-D-galactopyranosyl-D-glucopyranose, LacNAc) have been widely exploited as ligands for a wide range of galectins, sometimes with modest selectivity. Even though several chemical modifications at single positions of the sugar rings have been applied to these ligands, very few examples combined the simultaneous modifications at key positions known to increase both affinity and selectivity. We report herein combined modifications at the anomeric position, C-2, and O-3′ of each of the two sugars, resulting in a 3′-O-sulfated LacNAc analog having a Kd of 14.7 µM against human Gal-3 as measured by isothermal titration calorimetry (ITC). This represents a six-fold increase in affinity when compared to methyl β-D-lactoside having a Kd of 91 µM. The three best compounds contained sulfate groups at the O-3′ position of the galactoside moieties, which were perfectly in line with the observed highly cationic character of the human Gal-3 binding site shown by the co-crystal of one of the best candidates of the LacNAc series.
Fil: Abdullayev, Shuay. Université du Québec a Montreal; Canadá
Fil: Kadav, Priyanka. Michigan Technological University; Estados Unidos
Fil: Bandyopadhyay, Purnima. Michigan State University; Estados Unidos
Fil: Medrano, Francisco Javier. Centro de Investigaciones Bioquimicas Margarita Salas; España
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Dam, Tarun K.. Michigan Technological University; Estados Unidos
Fil: Romero, Antonio. Centro de Investigaciones Bioquimicas Margarita Salas; España
Fil: Roy, René. Université du Québec a Montreal; Canadá
Materia
GALECTIN
ISOTHERMAL TITRATION CALORIMETRY (ITC)
LACTOSIDE
X-RAY
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/216077
Acceder
id CONICETDig_c5585356ec6c0517d44a6d4cf2c4b298
oai_identifier_str oai:ri.conicet.gov.ar:11336/216077
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Selectively Modified Lactose and N-Acetyllactosamine Analogs at Three Key Positions to Afford Effective Galectin-3 LigandsAbdullayev, ShuayKadav, PriyankaBandyopadhyay, PurnimaMedrano, Francisco JavierRabinovich, Gabriel AdriánDam, Tarun K.Romero, AntonioRoy, RenéGALECTINISOTHERMAL TITRATION CALORIMETRY (ITC)LACTOSIDEX-RAYhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Galectins constitute a family of galactose-binding lectins overly expressed in the tumor microenvironment as well as in innate and adaptive immune cells, in inflammatory diseases. Lactose ((β-D-galactopyranosyl)-(1→4)-β-D-glucopyranose, Lac) and N-Acetyllactosamine (2-acetamido-2-deoxy-4-O-β-D-galactopyranosyl-D-glucopyranose, LacNAc) have been widely exploited as ligands for a wide range of galectins, sometimes with modest selectivity. Even though several chemical modifications at single positions of the sugar rings have been applied to these ligands, very few examples combined the simultaneous modifications at key positions known to increase both affinity and selectivity. We report herein combined modifications at the anomeric position, C-2, and O-3′ of each of the two sugars, resulting in a 3′-O-sulfated LacNAc analog having a Kd of 14.7 µM against human Gal-3 as measured by isothermal titration calorimetry (ITC). This represents a six-fold increase in affinity when compared to methyl β-D-lactoside having a Kd of 91 µM. The three best compounds contained sulfate groups at the O-3′ position of the galactoside moieties, which were perfectly in line with the observed highly cationic character of the human Gal-3 binding site shown by the co-crystal of one of the best candidates of the LacNAc series.Fil: Abdullayev, Shuay. Université du Québec a Montreal; CanadáFil: Kadav, Priyanka. Michigan Technological University; Estados UnidosFil: Bandyopadhyay, Purnima. Michigan State University; Estados UnidosFil: Medrano, Francisco Javier. Centro de Investigaciones Bioquimicas Margarita Salas; EspañaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Dam, Tarun K.. Michigan Technological University; Estados UnidosFil: Romero, Antonio. Centro de Investigaciones Bioquimicas Margarita Salas; EspañaFil: Roy, René. Université du Québec a Montreal; CanadáMolecular Diversity Preservation International2023-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/216077Abdullayev, Shuay; Kadav, Priyanka; Bandyopadhyay, Purnima; Medrano, Francisco Javier; Rabinovich, Gabriel Adrián; et al.; Selectively Modified Lactose and N-Acetyllactosamine Analogs at Three Key Positions to Afford Effective Galectin-3 Ligands; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 24; 4; 2-2023; 1-211422-0067CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/24/4/3718info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms24043718info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:04:11Zoai:ri.conicet.gov.ar:11336/216077instacron: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 10:04:11.414CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Selectively Modified Lactose and N-Acetyllactosamine Analogs at Three Key Positions to Afford Effective Galectin-3 Ligands
title Selectively Modified Lactose and N-Acetyllactosamine Analogs at Three Key Positions to Afford Effective Galectin-3 Ligands
spellingShingle Selectively Modified Lactose and N-Acetyllactosamine Analogs at Three Key Positions to Afford Effective Galectin-3 Ligands
Abdullayev, Shuay
GALECTIN
ISOTHERMAL TITRATION CALORIMETRY (ITC)
LACTOSIDE
X-RAY
title_short Selectively Modified Lactose and N-Acetyllactosamine Analogs at Three Key Positions to Afford Effective Galectin-3 Ligands
title_full Selectively Modified Lactose and N-Acetyllactosamine Analogs at Three Key Positions to Afford Effective Galectin-3 Ligands
title_fullStr Selectively Modified Lactose and N-Acetyllactosamine Analogs at Three Key Positions to Afford Effective Galectin-3 Ligands
title_full_unstemmed Selectively Modified Lactose and N-Acetyllactosamine Analogs at Three Key Positions to Afford Effective Galectin-3 Ligands
title_sort Selectively Modified Lactose and N-Acetyllactosamine Analogs at Three Key Positions to Afford Effective Galectin-3 Ligands
dc.creator.none.fl_str_mv Abdullayev, Shuay
Kadav, Priyanka
Bandyopadhyay, Purnima
Medrano, Francisco Javier
Rabinovich, Gabriel Adrián
Dam, Tarun K.
Romero, Antonio
Roy, René
author Abdullayev, Shuay
author_facet Abdullayev, Shuay
Kadav, Priyanka
Bandyopadhyay, Purnima
Medrano, Francisco Javier
Rabinovich, Gabriel Adrián
Dam, Tarun K.
Romero, Antonio
Roy, René
author_role author
author2 Kadav, Priyanka
Bandyopadhyay, Purnima
Medrano, Francisco Javier
Rabinovich, Gabriel Adrián
Dam, Tarun K.
Romero, Antonio
Roy, René
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv GALECTIN
ISOTHERMAL TITRATION CALORIMETRY (ITC)
LACTOSIDE
X-RAY
topic GALECTIN
ISOTHERMAL TITRATION CALORIMETRY (ITC)
LACTOSIDE
X-RAY
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Galectins constitute a family of galactose-binding lectins overly expressed in the tumor microenvironment as well as in innate and adaptive immune cells, in inflammatory diseases. Lactose ((β-D-galactopyranosyl)-(1→4)-β-D-glucopyranose, Lac) and N-Acetyllactosamine (2-acetamido-2-deoxy-4-O-β-D-galactopyranosyl-D-glucopyranose, LacNAc) have been widely exploited as ligands for a wide range of galectins, sometimes with modest selectivity. Even though several chemical modifications at single positions of the sugar rings have been applied to these ligands, very few examples combined the simultaneous modifications at key positions known to increase both affinity and selectivity. We report herein combined modifications at the anomeric position, C-2, and O-3′ of each of the two sugars, resulting in a 3′-O-sulfated LacNAc analog having a Kd of 14.7 µM against human Gal-3 as measured by isothermal titration calorimetry (ITC). This represents a six-fold increase in affinity when compared to methyl β-D-lactoside having a Kd of 91 µM. The three best compounds contained sulfate groups at the O-3′ position of the galactoside moieties, which were perfectly in line with the observed highly cationic character of the human Gal-3 binding site shown by the co-crystal of one of the best candidates of the LacNAc series.
Fil: Abdullayev, Shuay. Université du Québec a Montreal; Canadá
Fil: Kadav, Priyanka. Michigan Technological University; Estados Unidos
Fil: Bandyopadhyay, Purnima. Michigan State University; Estados Unidos
Fil: Medrano, Francisco Javier. Centro de Investigaciones Bioquimicas Margarita Salas; España
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Dam, Tarun K.. Michigan Technological University; Estados Unidos
Fil: Romero, Antonio. Centro de Investigaciones Bioquimicas Margarita Salas; España
Fil: Roy, René. Université du Québec a Montreal; Canadá
description Galectins constitute a family of galactose-binding lectins overly expressed in the tumor microenvironment as well as in innate and adaptive immune cells, in inflammatory diseases. Lactose ((β-D-galactopyranosyl)-(1→4)-β-D-glucopyranose, Lac) and N-Acetyllactosamine (2-acetamido-2-deoxy-4-O-β-D-galactopyranosyl-D-glucopyranose, LacNAc) have been widely exploited as ligands for a wide range of galectins, sometimes with modest selectivity. Even though several chemical modifications at single positions of the sugar rings have been applied to these ligands, very few examples combined the simultaneous modifications at key positions known to increase both affinity and selectivity. We report herein combined modifications at the anomeric position, C-2, and O-3′ of each of the two sugars, resulting in a 3′-O-sulfated LacNAc analog having a Kd of 14.7 µM against human Gal-3 as measured by isothermal titration calorimetry (ITC). This represents a six-fold increase in affinity when compared to methyl β-D-lactoside having a Kd of 91 µM. The three best compounds contained sulfate groups at the O-3′ position of the galactoside moieties, which were perfectly in line with the observed highly cationic character of the human Gal-3 binding site shown by the co-crystal of one of the best candidates of the LacNAc series.
publishDate 2023
dc.date.none.fl_str_mv 2023-02
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/11336/216077
Abdullayev, Shuay; Kadav, Priyanka; Bandyopadhyay, Purnima; Medrano, Francisco Javier; Rabinovich, Gabriel Adrián; et al.; Selectively Modified Lactose and N-Acetyllactosamine Analogs at Three Key Positions to Afford Effective Galectin-3 Ligands; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 24; 4; 2-2023; 1-21
1422-0067
CONICET Digital
CONICET
url http://hdl.handle.net/11336/216077
identifier_str_mv Abdullayev, Shuay; Kadav, Priyanka; Bandyopadhyay, Purnima; Medrano, Francisco Javier; Rabinovich, Gabriel Adrián; et al.; Selectively Modified Lactose and N-Acetyllactosamine Analogs at Three Key Positions to Afford Effective Galectin-3 Ligands; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 24; 4; 2-2023; 1-21
1422-0067
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/24/4/3718
info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms24043718
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
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_ 1842269842389860352
score 13.13397

Publicaciones similares