Improvement on binding of chondroitin sulfate derivatives to midkine by increasing hydrophobicity

The interactions between chondroitin sulfate (CS) and a wide number of proteins modulate important biological processes. Here, the binding properties to midkine and pleiotrophin of sulfated, fully protected intermediates, typically obtained in the chemical synthesis of CS oligosaccharides, were test...

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Detalles Bibliográficos
Autores: Paz, José L. de, Nieto, Pedro M.
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2016
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/75852
Acceso en línea:https://hdl.handle.net/11441/75852
https://doi.org/10.1039/c6ob00389c
Access Level:acceso abierto
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spelling Improvement on binding of chondroitin sulfate derivatives to midkine by increasing hydrophobicityPaz, José L. deNieto, Pedro M.The interactions between chondroitin sulfate (CS) and a wide number of proteins modulate important biological processes. Here, the binding properties to midkine and pleiotrophin of sulfated, fully protected intermediates, typically obtained in the chemical synthesis of CS oligosaccharides, were tested for the first time. Using a fluorescence polarization competition experiment, we discovered that these synthetic precursors strongly bound these two closely related cytokines involved in cancer and inflammation. The relative binding affinities of these intermediates were significantly higher than those displayed by the corresponding fully deprotected oligosaccharides, indicating that the presence of hydrophobic protecting groups strongly enhanced the binding of CS-like derivatives to midkine. These compounds offer novel opportunities for the development of potent inhibitors/activators of CS-protein interactions with potential therapeutic applications.Ministerio de Economía y Competitividad CTQ2012-32605Royal Society of ChemistryMinisterio de Economía y Competitividad (MINECO). España2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/75852https://doi.org/10.1039/c6ob00389creponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésOrganic and Biomolecular Chemistry, 14, 3506-3509.http://dx.doi.org/10.1039/c6ob00389cinfo:eu-repo/semantics/openAccessoai:idus.us.es:11441/758522026-06-17T12:51:07Z
dc.title.none.fl_str_mv Improvement on binding of chondroitin sulfate derivatives to midkine by increasing hydrophobicity
title Improvement on binding of chondroitin sulfate derivatives to midkine by increasing hydrophobicity
spellingShingle Improvement on binding of chondroitin sulfate derivatives to midkine by increasing hydrophobicity
Paz, José L. de
title_short Improvement on binding of chondroitin sulfate derivatives to midkine by increasing hydrophobicity
title_full Improvement on binding of chondroitin sulfate derivatives to midkine by increasing hydrophobicity
title_fullStr Improvement on binding of chondroitin sulfate derivatives to midkine by increasing hydrophobicity
title_full_unstemmed Improvement on binding of chondroitin sulfate derivatives to midkine by increasing hydrophobicity
title_sort Improvement on binding of chondroitin sulfate derivatives to midkine by increasing hydrophobicity
dc.creator.none.fl_str_mv Paz, José L. de
Nieto, Pedro M.
author Paz, José L. de
author_facet Paz, José L. de
Nieto, Pedro M.
author_role author
author2 Nieto, Pedro M.
author2_role author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (MINECO). España
description The interactions between chondroitin sulfate (CS) and a wide number of proteins modulate important biological processes. Here, the binding properties to midkine and pleiotrophin of sulfated, fully protected intermediates, typically obtained in the chemical synthesis of CS oligosaccharides, were tested for the first time. Using a fluorescence polarization competition experiment, we discovered that these synthetic precursors strongly bound these two closely related cytokines involved in cancer and inflammation. The relative binding affinities of these intermediates were significantly higher than those displayed by the corresponding fully deprotected oligosaccharides, indicating that the presence of hydrophobic protecting groups strongly enhanced the binding of CS-like derivatives to midkine. These compounds offer novel opportunities for the development of potent inhibitors/activators of CS-protein interactions with potential therapeutic applications.
publishDate 2016
dc.date.none.fl_str_mv 2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/75852
https://doi.org/10.1039/c6ob00389c
url https://hdl.handle.net/11441/75852
https://doi.org/10.1039/c6ob00389c
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Organic and Biomolecular Chemistry, 14, 3506-3509.
http://dx.doi.org/10.1039/c6ob00389c
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
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:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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