Artículo

Couto, A.S.; Soprano, L.L.; Landoni, M.; Pourcelot, M.; Acosta, D.M.; Bultel, L.; Parente, J.; Ferrero, M.R.; Barbier, M.; Dussouy, C.; Esteva, M.I.; Kovensky, J.; Duschak, V.G. "An anionic synthetic sugar containing 6-SO3-NAcGlc mimics the sulfated cruzipain epitope that plays a central role in immune recognition" (2012) FEBS Journal. 279(19):3665-3679
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Abstract:

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. A systematic study of the chemical characteristics needed for antibody binding to the cruzipain sulfated epitope was performed by immunoassays. Different molecules were synthesized, coupled to BSA/aprotinin, and confronted with rabbit/mice sera specific for Cz/C-T and purified IgGs from immune and human Chagas disease sera, demonstrating that synthetic GlcNAc6S mimics the N-glycan-linked-sulfated epitope displayed in the C-T domain of natural cruzipain. © 2012 The Authors Journal compilation © 2012 FEBS.

Registro:

Documento: Artículo
Título:An anionic synthetic sugar containing 6-SO3-NAcGlc mimics the sulfated cruzipain epitope that plays a central role in immune recognition
Autor:Couto, A.S.; Soprano, L.L.; Landoni, M.; Pourcelot, M.; Acosta, D.M.; Bultel, L.; Parente, J.; Ferrero, M.R.; Barbier, M.; Dussouy, C.; Esteva, M.I.; Kovensky, J.; Duschak, V.G.
Filiación:CIHIDECAR (CONICET), Departamento de Química Orgánica, Universidad de Buenos Aires, Argentina
Departamento de Investigación, Instituto Nacional de Parasitología Dr Mario Fatala Chaben, ANLIS-Malbrán Ministerio de Salud de la Nación, Paseo Colón 568, Ciudad de Buenos Aires (1063), Buenos Aires, Argentina
Laboratoire des Glucides, CNRS UMR 6219, Université de Picardie Jules Verne, Amiens, France
Palabras clave:cruzipain; epitope; glycoprotein; sulfated GlcNAc; Trypanosoma cruzi; acetic acid derivative; aprotinin; bovine serum albumin; cruzipain; disaccharide; immunoglobulin G; inorganic salt; monosaccharide; n acetyl dextro glucosamine 6 sulfate sodium salt; oligosaccharide; sulfate; unclassified drug; adult; animal experiment; antibody production; antigen binding; antigen recognition; article; binding affinity; carboxy terminal sequence; carboxylation; Chagas disease; competitive inhibition; controlled study; enzyme modification; enzyme structure; esterification; female; human; immunization; immunoassay; mouse; nonhuman; nucleotide sequence; phosphorylation; priority journal; rabbit; structure activity relation; sulfation; surface charge; Trypanosoma cruzi; Acetylglucosamine; Adolescent; Adult; Animals; Anions; Case-Control Studies; Chagas Disease; Cysteine Endopeptidases; Enzyme-Linked Immunosorbent Assay; Epitopes; Female; Humans; Immunoglobulin G; Magnetic Resonance Spectroscopy; Male; Mice; Mice, Inbred BALB C; Middle Aged; Oligosaccharides; Rabbits; Serologic Tests; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Sulfates; Trypanosoma cruzi; Young Adult; Oryctolagus cuniculus; Trypanosoma cruzi
Año:2012
Volumen:279
Número:19
Página de inicio:3665
Página de fin:3679
DOI: http://dx.doi.org/10.1111/j.1742-4658.2012.08728.x
Título revista:FEBS Journal
Título revista abreviado:FEBS J.
ISSN:1742464X
CODEN:FJEOA
CAS:aprotinin, 11004-21-0, 12407-79-3, 50936-63-5, 52229-70-6, 58591-29-0, 9050-74-2, 9075-10-9, 9087-70-1; immunoglobulin G, 97794-27-9; sulfate, 14808-79-8; Acetylglucosamine, 7512-17-6; Anions; Cysteine Endopeptidases, 3.4.22.-; Epitopes; Immunoglobulin G; Oligosaccharides; Sulfates; cruzipain, 3.4.22.-
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_1742464X_v279_n19_p3665_Couto

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Citas:

---------- APA ----------
Couto, A.S., Soprano, L.L., Landoni, M., Pourcelot, M., Acosta, D.M., Bultel, L., Parente, J.,..., Duschak, V.G. (2012) . An anionic synthetic sugar containing 6-SO3-NAcGlc mimics the sulfated cruzipain epitope that plays a central role in immune recognition. FEBS Journal, 279(19), 3665-3679.
http://dx.doi.org/10.1111/j.1742-4658.2012.08728.x
---------- CHICAGO ----------
Couto, A.S., Soprano, L.L., Landoni, M., Pourcelot, M., Acosta, D.M., Bultel, L., et al. "An anionic synthetic sugar containing 6-SO3-NAcGlc mimics the sulfated cruzipain epitope that plays a central role in immune recognition" . FEBS Journal 279, no. 19 (2012) : 3665-3679.
http://dx.doi.org/10.1111/j.1742-4658.2012.08728.x
---------- MLA ----------
Couto, A.S., Soprano, L.L., Landoni, M., Pourcelot, M., Acosta, D.M., Bultel, L., et al. "An anionic synthetic sugar containing 6-SO3-NAcGlc mimics the sulfated cruzipain epitope that plays a central role in immune recognition" . FEBS Journal, vol. 279, no. 19, 2012, pp. 3665-3679.
http://dx.doi.org/10.1111/j.1742-4658.2012.08728.x
---------- VANCOUVER ----------
Couto, A.S., Soprano, L.L., Landoni, M., Pourcelot, M., Acosta, D.M., Bultel, L., et al. An anionic synthetic sugar containing 6-SO3-NAcGlc mimics the sulfated cruzipain epitope that plays a central role in immune recognition. FEBS J. 2012;279(19):3665-3679.
http://dx.doi.org/10.1111/j.1742-4658.2012.08728.x