Synthesis of a model trisaccharide for studying the interplay between the anti α-Gal antibody and the trans-sialidase reactions in Trypanosoma cruzi
Trypanosoma cruzi, the etiologic agent of Chagas disease, is covered by a dense glycocalix mainly composed by glycoproteins called mucins which are also the acceptors of sialic acid in a reaction catalyzed by a trans-sialidase (TcTS). Sialylation of trypomastigote mucins protects the parasite from l...
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todo:paper_00086215_v450_n_p30_Giorgi2023-10-03T14:07:35Z Synthesis of a model trisaccharide for studying the interplay between the anti α-Gal antibody and the trans-sialidase reactions in Trypanosoma cruzi Giorgi, M.E. Lopez, R. Agusti, R. Marino, C. de Lederkremer, R.M. Anti α-gal Trans-sialidase Trypanosoma cruzi Carboxylic acids Biochemical studies Etiologic agents Infection process Reaction catalyzed Synthetic approach Trans-sialidases Trypanosoma cruzi Virulent strains Antibodies 6 aminohexyl glycoside glycoside sialidase trisaccharide unclassified drug antibody calcium binding protein galactose-binding protein glucose transporter glycoprotein periplasmic binding protein sialidase trans-sialidase trisaccharide Article biochemical analysis carbohydrate synthesis conjugation nonhuman priority journal sialylation Trypanosoma cruzi carbohydrate analysis chemistry immunology metabolism synthesis Trypanosoma cruzi Antibodies Calcium-Binding Proteins Carbohydrate Sequence Chemistry Techniques, Synthetic Glycoproteins Monosaccharide Transport Proteins Neuraminidase Periplasmic Binding Proteins Trisaccharides Trypanosoma cruzi Trypanosoma cruzi, the etiologic agent of Chagas disease, is covered by a dense glycocalix mainly composed by glycoproteins called mucins which are also the acceptors of sialic acid in a reaction catalyzed by a trans-sialidase (TcTS). Sialylation of trypomastigote mucins protects the parasite from lysis by the anti α-Galp antibodies from serum. The TcTS is essential for the infection process since T. cruzi is unable to biosynthesize sialic acid. The enzyme specifically transfers it from a terminal β-D-Galp unit in the host glycoconjugate to terminal β-D-Galp units in the parasite mucins to construct the D-NeuNAc(α2→3)β-D-Galp motif. On the other hand, although galactose is the most abundant sugar in mucins of both, the infective trypomastigotes and the insect stage epimastigotes, α-D-Galp is only present in the infective stage whereas β-D-Galf is characteristic of the epimastigote stage of the less virulent strains. Neither α-D-Galp nor D-Galf is acceptor of sialic acid. In the mucins, some of the oligosaccharides are branched with terminal β-D-Galp units to be able to accept sialic acid in the TcTS reaction. Based on previous reports showing that anti α-Galp antibodies only partially colocalize with sialic acid, we have undertaken the synthesis of the trisaccharide α-D-Galp(1→3)-[β-D-Galp(1→6)]-D-Galp, the smallest structure containing both, the antigenic D-Galp(α1→3)-D-Galp unit and the sialic acid-acceptor β-D-Galp unit. The trisaccharide was obtained as the 6-aminohexyl glycoside to facilitate further conjugation for biochemical studies. The synthetic approach involved the α-galactosylation at O-4 of a suitable precursor of the reducing end, followed by β-galactosylation at O-6 of the same precursor and introduction of the 6-aminohexyl aglycone. The fully deprotected trisaccharide was successfully sialylated by TcTS using either 3′-sialyllactose or fetuin as donors. The product, 6-aminohexyl α-D-NeuNAc(2→3)-β-D-Galp(1→6)-[α-D-Galp(1→3)]-β-D-Galp, was purified and characterized. © 2017 Elsevier Ltd JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00086215_v450_n_p30_Giorgi |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Anti α-gal Trans-sialidase Trypanosoma cruzi Carboxylic acids Biochemical studies Etiologic agents Infection process Reaction catalyzed Synthetic approach Trans-sialidases Trypanosoma cruzi Virulent strains Antibodies 6 aminohexyl glycoside glycoside sialidase trisaccharide unclassified drug antibody calcium binding protein galactose-binding protein glucose transporter glycoprotein periplasmic binding protein sialidase trans-sialidase trisaccharide Article biochemical analysis carbohydrate synthesis conjugation nonhuman priority journal sialylation Trypanosoma cruzi carbohydrate analysis chemistry immunology metabolism synthesis Trypanosoma cruzi Antibodies Calcium-Binding Proteins Carbohydrate Sequence Chemistry Techniques, Synthetic Glycoproteins Monosaccharide Transport Proteins Neuraminidase Periplasmic Binding Proteins Trisaccharides Trypanosoma cruzi |
| spellingShingle |
Anti α-gal Trans-sialidase Trypanosoma cruzi Carboxylic acids Biochemical studies Etiologic agents Infection process Reaction catalyzed Synthetic approach Trans-sialidases Trypanosoma cruzi Virulent strains Antibodies 6 aminohexyl glycoside glycoside sialidase trisaccharide unclassified drug antibody calcium binding protein galactose-binding protein glucose transporter glycoprotein periplasmic binding protein sialidase trans-sialidase trisaccharide Article biochemical analysis carbohydrate synthesis conjugation nonhuman priority journal sialylation Trypanosoma cruzi carbohydrate analysis chemistry immunology metabolism synthesis Trypanosoma cruzi Antibodies Calcium-Binding Proteins Carbohydrate Sequence Chemistry Techniques, Synthetic Glycoproteins Monosaccharide Transport Proteins Neuraminidase Periplasmic Binding Proteins Trisaccharides Trypanosoma cruzi Giorgi, M.E. Lopez, R. Agusti, R. Marino, C. de Lederkremer, R.M. Synthesis of a model trisaccharide for studying the interplay between the anti α-Gal antibody and the trans-sialidase reactions in Trypanosoma cruzi |
| topic_facet |
Anti α-gal Trans-sialidase Trypanosoma cruzi Carboxylic acids Biochemical studies Etiologic agents Infection process Reaction catalyzed Synthetic approach Trans-sialidases Trypanosoma cruzi Virulent strains Antibodies 6 aminohexyl glycoside glycoside sialidase trisaccharide unclassified drug antibody calcium binding protein galactose-binding protein glucose transporter glycoprotein periplasmic binding protein sialidase trans-sialidase trisaccharide Article biochemical analysis carbohydrate synthesis conjugation nonhuman priority journal sialylation Trypanosoma cruzi carbohydrate analysis chemistry immunology metabolism synthesis Trypanosoma cruzi Antibodies Calcium-Binding Proteins Carbohydrate Sequence Chemistry Techniques, Synthetic Glycoproteins Monosaccharide Transport Proteins Neuraminidase Periplasmic Binding Proteins Trisaccharides Trypanosoma cruzi |
| description |
Trypanosoma cruzi, the etiologic agent of Chagas disease, is covered by a dense glycocalix mainly composed by glycoproteins called mucins which are also the acceptors of sialic acid in a reaction catalyzed by a trans-sialidase (TcTS). Sialylation of trypomastigote mucins protects the parasite from lysis by the anti α-Galp antibodies from serum. The TcTS is essential for the infection process since T. cruzi is unable to biosynthesize sialic acid. The enzyme specifically transfers it from a terminal β-D-Galp unit in the host glycoconjugate to terminal β-D-Galp units in the parasite mucins to construct the D-NeuNAc(α2→3)β-D-Galp motif. On the other hand, although galactose is the most abundant sugar in mucins of both, the infective trypomastigotes and the insect stage epimastigotes, α-D-Galp is only present in the infective stage whereas β-D-Galf is characteristic of the epimastigote stage of the less virulent strains. Neither α-D-Galp nor D-Galf is acceptor of sialic acid. In the mucins, some of the oligosaccharides are branched with terminal β-D-Galp units to be able to accept sialic acid in the TcTS reaction. Based on previous reports showing that anti α-Galp antibodies only partially colocalize with sialic acid, we have undertaken the synthesis of the trisaccharide α-D-Galp(1→3)-[β-D-Galp(1→6)]-D-Galp, the smallest structure containing both, the antigenic D-Galp(α1→3)-D-Galp unit and the sialic acid-acceptor β-D-Galp unit. The trisaccharide was obtained as the 6-aminohexyl glycoside to facilitate further conjugation for biochemical studies. The synthetic approach involved the α-galactosylation at O-4 of a suitable precursor of the reducing end, followed by β-galactosylation at O-6 of the same precursor and introduction of the 6-aminohexyl aglycone. The fully deprotected trisaccharide was successfully sialylated by TcTS using either 3′-sialyllactose or fetuin as donors. The product, 6-aminohexyl α-D-NeuNAc(2→3)-β-D-Galp(1→6)-[α-D-Galp(1→3)]-β-D-Galp, was purified and characterized. © 2017 Elsevier Ltd |
| format |
JOUR |
| author |
Giorgi, M.E. Lopez, R. Agusti, R. Marino, C. de Lederkremer, R.M. |
| author_facet |
Giorgi, M.E. Lopez, R. Agusti, R. Marino, C. de Lederkremer, R.M. |
| author_sort |
Giorgi, M.E. |
| title |
Synthesis of a model trisaccharide for studying the interplay between the anti α-Gal antibody and the trans-sialidase reactions in Trypanosoma cruzi |
| title_short |
Synthesis of a model trisaccharide for studying the interplay between the anti α-Gal antibody and the trans-sialidase reactions in Trypanosoma cruzi |
| title_full |
Synthesis of a model trisaccharide for studying the interplay between the anti α-Gal antibody and the trans-sialidase reactions in Trypanosoma cruzi |
| title_fullStr |
Synthesis of a model trisaccharide for studying the interplay between the anti α-Gal antibody and the trans-sialidase reactions in Trypanosoma cruzi |
| title_full_unstemmed |
Synthesis of a model trisaccharide for studying the interplay between the anti α-Gal antibody and the trans-sialidase reactions in Trypanosoma cruzi |
| title_sort |
synthesis of a model trisaccharide for studying the interplay between the anti α-gal antibody and the trans-sialidase reactions in trypanosoma cruzi |
| url |
http://hdl.handle.net/20.500.12110/paper_00086215_v450_n_p30_Giorgi |
| work_keys_str_mv |
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1782027325332783104 |