Selectively modified lactose and N-acetyllactosamine analogs at three key positions to afford effective galectin-3 ligands

21 p,-3 fig.-2 tab.4 schem.

Detalhes bibliográficos
Autores: Abdullayev, Shuay, Kadav, Priyanka, Bandyopadhyay, Purnima, Medrano, Francisco Javier, Rabinovich, Gabriel A., Dam, Tarun K., Romero, Antonio, Roy, René
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:dnet:digitalcsic_::c746040634d6565cf4a9af6e16d25f49
Acesso em linha:http://hdl.handle.net/10261/349580
Access Level:acceso abierto
Palavra-chave:Galectin
Lactoside
Isothermal titration calorimetry (ITC)
X-ray
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spelling Selectively modified lactose and N-acetyllactosamine analogs at three key positions to afford effective galectin-3 ligandsAbdullayev, ShuayKadav, PriyankaBandyopadhyay, PurnimaMedrano, Francisco JavierRabinovich, Gabriel A.Dam, Tarun K.Romero, AntonioRoy, RenéGalectinLactosideIsothermal titration calorimetry (ITC)X-ray21 p,-3 fig.-2 tab.4 schem.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.This work was supported by the Natural Science and Engineering Research Council of Canada (NSERC) (to R.R.) including a Canadian Research Chair and the Fonds du Québec–Nature et Technologies (to R.R.), the National Science Foundation, grant number 1608537 (to T.K.D.), the Agencia de Investigación, Desarrollo e Innovación, grant numbers 2017-0494 and PICT 2020-01552 (to G.A.R.), the Bunge and Born Foundation, the Sales Foundation, and The Richard Lounsbery Foundation (to G.A.R.), and by the Consejo Superior de Investigaciones Científicas, grant number PIE-202020E224 (to A.R.).Peer reviewedMultidisciplinary Digital Publishing InstituteNatural Sciences and Engineering Research Council of CanadaNational Science Foundation (US)Agencia Estatal de Investigación (España)Bunge & Born FoundationFundación SalesRichard Lounsbery FoundationConsejo Superior de Investigaciones Científicas (España)Abdullayev, Shuay [0000-0002-3965-7785]Medrano, Francisco Javier [0000-0002-8185-9751]Rabinovich, Gabriel A. [0000-0002-0947-8735]Dam, Tarun K. [0009-0008-3548-1007]Romero, Antonio [0000-0002-6990-6973]Roy, René [0000-0001-5638-7302]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/349580reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.3390/ijms24043718Síinfo:eu-repo/semantics/openAccessoai:dnet:digitalcsic_::c746040634d6565cf4a9af6e16d25f492026-05-22T06:33:51Z
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
Lactoside
Isothermal titration calorimetry (ITC)
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 A.
Dam, Tarun K.
Romero, Antonio
Roy, René
author Abdullayev, Shuay
author_facet Abdullayev, Shuay
Kadav, Priyanka
Bandyopadhyay, Purnima
Medrano, Francisco Javier
Rabinovich, Gabriel A.
Dam, Tarun K.
Romero, Antonio
Roy, René
author_role author
author2 Kadav, Priyanka
Bandyopadhyay, Purnima
Medrano, Francisco Javier
Rabinovich, Gabriel A.
Dam, Tarun K.
Romero, Antonio
Roy, René
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Natural Sciences and Engineering Research Council of Canada
National Science Foundation (US)
Agencia Estatal de Investigación (España)
Bunge & Born Foundation
Fundación Sales
Richard Lounsbery Foundation
Consejo Superior de Investigaciones Científicas (España)
Abdullayev, Shuay [0000-0002-3965-7785]
Medrano, Francisco Javier [0000-0002-8185-9751]
Rabinovich, Gabriel A. [0000-0002-0947-8735]
Dam, Tarun K. [0009-0008-3548-1007]
Romero, Antonio [0000-0002-6990-6973]
Roy, René [0000-0001-5638-7302]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Galectin
Lactoside
Isothermal titration calorimetry (ITC)
X-ray
topic Galectin
Lactoside
Isothermal titration calorimetry (ITC)
X-ray
description 21 p,-3 fig.-2 tab.4 schem.
publishDate 2023
dc.date.none.fl_str_mv 2023
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/349580
url http://hdl.handle.net/10261/349580
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.3390/ijms24043718
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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