An anionic synthetic sugar containing 6-SO3-NAcGlc mimics the sulfated cruzipain epitope that plays a central role in immune recognition

Autores
Couto, Alicia S.; Soprano, Luciana L.; Landoni, Malena; Pourcelot, Marilyne; Acosta, Diana M.; Bultel, Laurent; Parente, Juliana Elena; Ferrero, Maximiliano R.; Barbier, Maximilien; Dussouy, Christophe; Esteva, Mónica I.; Kovensky, José; Duschak, Vilma G.
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión enviada
Descripción
Cruzipain (Cz), the major cysteine proteinase of Trypanosoma cruzi, is a glycoprotein that contains sulfated high-mannose-type oligosaccharides. We have previously determined that these sulfate groups are targets of specific immune responses. In order to evaluate the structural requirements for antibody recognition of Cz, a systematic structure–activity study of the chemical characteristics needed for antibody binding to the Cz sulfated epitope was performed by immunoassays. With this aim, different synthesized molecules were coupled to the proteins BSA and aprotinin and confronted with (a) mouse sera specific for Cz and its carboxy-terminal (C-T) domain, (b) antibodies raised in rabbits immunized with Cz and its C-terminal domain and (c) IgGs purified from human Chagas disease sera. Our results indicate that a glucosamine containing an esterifying sulfate group in position O-6 and an N-acetyl group was the preferred epitope for the immune recognition of sera specific for Cz and its C-T domain. Although to a minor extent, other anionic compounds bearing sulfate groups in different positions and number as well as different anionic charged groups including carboxylated or phosphorylated monosaccharides, disaccharides and oligosaccharides were recognized. In conclusion, we found that synthetic anionic sugar conjugates containing N-acetyl D-glucosamine-6-sulfate sodium salt (GlcNAc6S) competitively inhibit the binding of affinity purified rabbit anti-C-T IgG to the C-T extension of Cz. Extending these findings to the context of natural infection, immune assays performed with Chagas disease serum confirmed that the structure of synthetic GlcNAc6S mimics the N-glycan-linked sulfated epitope displayed in the C-T domain of Cz.
Materia
Ciencias Químicas
Cruzipain
Trypanosoma cruzi
sulfated high-mannose-type oligosaccharides
immunoassays
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-nd/4.0/
Repositorio
CIC Digital (CICBA)
Institución
Comisión de Investigaciones Científicas de la Provincia de Buenos Aires
OAI Identificador
oai:digital.cic.gba.gob.ar:11746/8273

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network_acronym_str CICBA
repository_id_str 9441
network_name_str CIC Digital (CICBA)
spelling An anionic synthetic sugar containing 6-SO3-NAcGlc mimics the sulfated cruzipain epitope that plays a central role in immune recognitionCouto, Alicia S.Soprano, Luciana L.Landoni, MalenaPourcelot, MarilyneAcosta, Diana M.Bultel, LaurentParente, Juliana ElenaFerrero, Maximiliano R.Barbier, MaximilienDussouy, ChristopheEsteva, Mónica I.Kovensky, JoséDuschak, Vilma G.Ciencias QuímicasCruzipainTrypanosoma cruzisulfated high-mannose-type oligosaccharidesimmunoassaysCruzipain (Cz), the major cysteine proteinase of <em>Trypanosoma cruzi</em>, is a glycoprotein that contains sulfated high-mannose-type oligosaccharides. We have previously determined that these sulfate groups are targets of specific immune responses. In order to evaluate the structural requirements for antibody recognition of Cz, a systematic structure–activity study of the chemical characteristics needed for antibody binding to the Cz sulfated epitope was performed by immunoassays. With this aim, different synthesized molecules were coupled to the proteins BSA and aprotinin and confronted with (a) mouse sera specific for Cz and its carboxy-terminal (C-T) domain, (b) antibodies raised in rabbits immunized with Cz and its C-terminal domain and (c) IgGs purified from human Chagas disease sera. Our results indicate that a glucosamine containing an esterifying sulfate group in position O-6 and an N-acetyl group was the preferred epitope for the immune recognition of sera specific for Cz and its C-T domain. Although to a minor extent, other anionic compounds bearing sulfate groups in different positions and number as well as different anionic charged groups including carboxylated or phosphorylated monosaccharides, disaccharides and oligosaccharides were recognized. In conclusion, we found that synthetic anionic sugar conjugates containing N-acetyl D-glucosamine-6-sulfate sodium salt (GlcNAc6S) competitively inhibit the binding of affinity purified rabbit anti-C-T IgG to the C-T extension of Cz. Extending these findings to the context of natural infection, immune assays performed with Chagas disease serum confirmed that the structure of synthetic GlcNAc6S mimics the N-glycan-linked sulfated epitope displayed in the C-T domain of Cz.2012-07-23info:eu-repo/semantics/articleinfo:eu-repo/semantics/submittedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://digital.cic.gba.gob.ar/handle/11746/8273enginfo:eu-repo/semantics/altIdentifier/doi/10.1111/j.1742-4658.2012.08728.xinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-nd/4.0/reponame:CIC Digital (CICBA)instname:Comisión de Investigaciones Científicas de la Provincia de Buenos Airesinstacron:CICBA2025-09-04T09:43:05Zoai:digital.cic.gba.gob.ar:11746/8273Institucionalhttp://digital.cic.gba.gob.arOrganismo científico-tecnológicoNo correspondehttp://digital.cic.gba.gob.ar/oai/snrdmarisa.degiusti@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:94412025-09-04 09:43:07.043CIC Digital (CICBA) - Comisión de Investigaciones Científicas de la Provincia de Buenos Airesfalse
dc.title.none.fl_str_mv An anionic synthetic sugar containing 6-SO3-NAcGlc mimics the sulfated cruzipain epitope that plays a central role in immune recognition
title An anionic synthetic sugar containing 6-SO3-NAcGlc mimics the sulfated cruzipain epitope that plays a central role in immune recognition
spellingShingle An anionic synthetic sugar containing 6-SO3-NAcGlc mimics the sulfated cruzipain epitope that plays a central role in immune recognition
Couto, Alicia S.
Ciencias Químicas
Cruzipain
Trypanosoma cruzi
sulfated high-mannose-type oligosaccharides
immunoassays
title_short An anionic synthetic sugar containing 6-SO3-NAcGlc mimics the sulfated cruzipain epitope that plays a central role in immune recognition
title_full An anionic synthetic sugar containing 6-SO3-NAcGlc mimics the sulfated cruzipain epitope that plays a central role in immune recognition
title_fullStr An anionic synthetic sugar containing 6-SO3-NAcGlc mimics the sulfated cruzipain epitope that plays a central role in immune recognition
title_full_unstemmed An anionic synthetic sugar containing 6-SO3-NAcGlc mimics the sulfated cruzipain epitope that plays a central role in immune recognition
title_sort An anionic synthetic sugar containing 6-SO3-NAcGlc mimics the sulfated cruzipain epitope that plays a central role in immune recognition
dc.creator.none.fl_str_mv Couto, Alicia S.
Soprano, Luciana L.
Landoni, Malena
Pourcelot, Marilyne
Acosta, Diana M.
Bultel, Laurent
Parente, Juliana Elena
Ferrero, Maximiliano R.
Barbier, Maximilien
Dussouy, Christophe
Esteva, Mónica I.
Kovensky, José
Duschak, Vilma G.
author Couto, Alicia S.
author_facet Couto, Alicia S.
Soprano, Luciana L.
Landoni, Malena
Pourcelot, Marilyne
Acosta, Diana M.
Bultel, Laurent
Parente, Juliana Elena
Ferrero, Maximiliano R.
Barbier, Maximilien
Dussouy, Christophe
Esteva, Mónica I.
Kovensky, José
Duschak, Vilma G.
author_role author
author2 Soprano, Luciana L.
Landoni, Malena
Pourcelot, Marilyne
Acosta, Diana M.
Bultel, Laurent
Parente, Juliana Elena
Ferrero, Maximiliano R.
Barbier, Maximilien
Dussouy, Christophe
Esteva, Mónica I.
Kovensky, José
Duschak, Vilma G.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Químicas
Cruzipain
Trypanosoma cruzi
sulfated high-mannose-type oligosaccharides
immunoassays
topic Ciencias Químicas
Cruzipain
Trypanosoma cruzi
sulfated high-mannose-type oligosaccharides
immunoassays
dc.description.none.fl_txt_mv Cruzipain (Cz), the major cysteine proteinase of <em>Trypanosoma cruzi</em>, is a glycoprotein that contains sulfated high-mannose-type oligosaccharides. We have previously determined that these sulfate groups are targets of specific immune responses. In order to evaluate the structural requirements for antibody recognition of Cz, a systematic structure–activity study of the chemical characteristics needed for antibody binding to the Cz sulfated epitope was performed by immunoassays. With this aim, different synthesized molecules were coupled to the proteins BSA and aprotinin and confronted with (a) mouse sera specific for Cz and its carboxy-terminal (C-T) domain, (b) antibodies raised in rabbits immunized with Cz and its C-terminal domain and (c) IgGs purified from human Chagas disease sera. Our results indicate that a glucosamine containing an esterifying sulfate group in position O-6 and an N-acetyl group was the preferred epitope for the immune recognition of sera specific for Cz and its C-T domain. Although to a minor extent, other anionic compounds bearing sulfate groups in different positions and number as well as different anionic charged groups including carboxylated or phosphorylated monosaccharides, disaccharides and oligosaccharides were recognized. In conclusion, we found that synthetic anionic sugar conjugates containing N-acetyl D-glucosamine-6-sulfate sodium salt (GlcNAc6S) competitively inhibit the binding of affinity purified rabbit anti-C-T IgG to the C-T extension of Cz. Extending these findings to the context of natural infection, immune assays performed with Chagas disease serum confirmed that the structure of synthetic GlcNAc6S mimics the N-glycan-linked sulfated epitope displayed in the C-T domain of Cz.
description Cruzipain (Cz), the major cysteine proteinase of <em>Trypanosoma cruzi</em>, is a glycoprotein that contains sulfated high-mannose-type oligosaccharides. We have previously determined that these sulfate groups are targets of specific immune responses. In order to evaluate the structural requirements for antibody recognition of Cz, a systematic structure–activity study of the chemical characteristics needed for antibody binding to the Cz sulfated epitope was performed by immunoassays. With this aim, different synthesized molecules were coupled to the proteins BSA and aprotinin and confronted with (a) mouse sera specific for Cz and its carboxy-terminal (C-T) domain, (b) antibodies raised in rabbits immunized with Cz and its C-terminal domain and (c) IgGs purified from human Chagas disease sera. Our results indicate that a glucosamine containing an esterifying sulfate group in position O-6 and an N-acetyl group was the preferred epitope for the immune recognition of sera specific for Cz and its C-T domain. Although to a minor extent, other anionic compounds bearing sulfate groups in different positions and number as well as different anionic charged groups including carboxylated or phosphorylated monosaccharides, disaccharides and oligosaccharides were recognized. In conclusion, we found that synthetic anionic sugar conjugates containing N-acetyl D-glucosamine-6-sulfate sodium salt (GlcNAc6S) competitively inhibit the binding of affinity purified rabbit anti-C-T IgG to the C-T extension of Cz. Extending these findings to the context of natural infection, immune assays performed with Chagas disease serum confirmed that the structure of synthetic GlcNAc6S mimics the N-glycan-linked sulfated epitope displayed in the C-T domain of Cz.
publishDate 2012
dc.date.none.fl_str_mv 2012-07-23
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/submittedVersion
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info:ar-repo/semantics/articulo
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status_str submittedVersion
dc.identifier.none.fl_str_mv https://digital.cic.gba.gob.ar/handle/11746/8273
url https://digital.cic.gba.gob.ar/handle/11746/8273
dc.language.none.fl_str_mv eng
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dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1742-4658.2012.08728.x
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
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