Taxonomic group: protista / Euglenozoa
(Phylum: Euglenozoa)
Host organism: (mammal)
Organ / tissue: Life stage: trypomastigoteAssociated disease: Chagas disease [ICD11:
1F53 
, ICD11:
XN56V ];
infection due to Trypanosoma cruzi [ICD11:
XN56V ]
The structure was elucidated in this paperNCBI PubMed ID: 28858610Publication DOI: 10.1016/j.carres.2017.08.007Journal NLM ID: 0043535Publisher: Elsevier
Correspondence: lederk
qo.fcen.uba.ar; cmarino
qo.fcen.uba.ar
Institutions: Universidad de Buenos Aires, Consejo Nacional de Investigaciones Cientificas y Técnicas, Centro de Investigaciones en Hidratos de Carbono (CIHIDECAR), Facultad de Ciencias Exactas y Naturales, Departamento de Química Orgánica, Buenos Aires, Argentina
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.
sialic acid, Trypanosoma cruzi, mucins, trans-sialidase, Anti α-gal
Structure type: oligomer ; 1098.50671 [M+H]+
C
60H
75NO
18Location inside paper: abstract, p. 31, Scheme 2, compound 1
Aglycon: 6-aminohexanol
Trivial name: mucin oligosaccharide, α-gal epitope
Compound class: O-glycan
Contained glycoepitopes: IEDB_115013,IEDB_130645,IEDB_136044,IEDB_136906,IEDB_137472,IEDB_141794,IEDB_149558,IEDB_151528,IEDB_153201,IEDB_156493,IEDB_190606,IEDB_918314,SB_165,SB_166,SB_187,SB_195,SB_7,SB_87,SB_88
Methods: 13C NMR, 1H NMR, NMR-2D, TLC, ESI-MS, chemical synthesis, HPLC, HPAEC-PAD, sialylation, CC
Synthetic data: chemical
Related record ID(s): 4519, 7304
NCBI Taxonomy refs (TaxIDs): 5693
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There is only one chemically distinct structure:
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