Taxonomic group: protista / Euglenozoa
(Phylum: Euglenozoa)
Host organism: Homo sapiens
Associated disease: infection due to Leishmania major [ICD11:
XN7EU 
];
infection due to Leishmania tropica [ICD11:
XN95N ];
cutaneous leishmaniasis [ICD11:
1F54.1 , ICD11:
XN8JE ]
The structure was elucidated in this paperNCBI PubMed ID: 34467365Publication DOI: 10.1021/jacsau.1c00201Journal NLM ID: 101775714Publisher: Washington, DC: American Chemical Society
Correspondence: alvaro.acosta-serrano
lstmed.ac.uk; calmeida
utep.edu; kmichael
utep.edu
Institutions: Department of Chemistry and Biochemistry, Border Biomedical Research Center, University of Texas at El Paso, 500 West University Avenue, El Paso, Texas 79968, United States, Department of Vector Biology, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, United Kingdom, Department of Biological Sciences, Border Biomedical Research Center, University of Texas at El Paso, 500 West University Avenue, El Paso, Texas 79968, United States
All healthy humans have high levels of natural anti-α-galactosyl (α-Gal) antibodies (elicited by yet uncharacterized glycotopes), which may play important roles in immunoglycomics: (a) potential protection against certain parasitic and viral zoonotic infections; (b) targeting of α-Gal-engineered cancer cells; (c) aiding in tissue repair; and (d) serving as adjuvants in α-Gal-based vaccines. Patients with certain protozoan infections have specific anti-α-Gal antibodies, elicited against parasite-derived α-Gal-bearing glycotopes. These glycotopes, however, remain elusive except for the well-characterized glycotope Galα1,3Galβ1,4GlcNAcα, expressed by Trypanosoma cruzi. The discovery of new parasitic glycotopes is greatly hindered by the enormous structural diversity of cell-surface glycans and the technical challenges of classical immunoglycomics, a top-down approach from cultivated parasites to isolated glycans. Here, we demonstrate that reversed immunoglycomics, a bottom-up approach, can identify parasite species-specific α-Gal-bearing glycotopes by probing synthetic oligosaccharides on neoglycoproteins. This method was tested here seeking to identify as-yet unknown glycotopes specific for Leishmania major, the causative agent of Old-World cutaneous leishmaniasis (OWCL). Neoglycoproteins decorated with synthetic α-Gal-containing oligosaccharides derived from L. major glycoinositolphospholipids served as antigens in a chemiluminescent enzyme-linked immunosorbent assay using sera from OWCL patients and noninfected individuals. Receiver-operating characteristic analysis identified Galpα1,3Galfβ and Galpα1,3Galfβ1,3Manpα glycotopes as diagnostic biomarkers for L. major-caused OWCL, which can distinguish with 100% specificity from heterologous diseases and L. tropica-caused OWCL. These glycotopes could prove useful in the development of rapid α-Gal-based diagnostics and vaccines for OWCL. Furthermore, this method could help unravel cryptic α-Gal-glycotopes of other protozoan parasites and enterobacteria that elicit the natural human anti-α-Gal antibodies.
antigen, oligosaccharide synthesis, neoglycoproteins, Bioorganic chemistry, glycoinositolphospholipids, biomarkers, cutaneous leishmaniasis, anti-α-Gal antibodies, Leishmania major
Structure type: fragment of a bigger structure
Location inside paper: p.1282, NPG27b
Aglycon: BSA
Trivial name: α-gal epitope, type-2 GIPL
Compound class: neoglycoconjugate
Contained glycoepitopes: IEDB_136095,IEDB_136906,IEDB_137472,IEDB_141794,IEDB_151528,IEDB_190606,SB_7
Methods: chemical synthesis, chemical methods, MALDI-TOF MS, serological methods, ESI-TOF-MS, conjugation, chemiluminescent ELISA, immunoglycomics studies
Synthetic data: chemical
Comments, role: the terminal disaccharide of GIPL-2.
Related record ID(s): 7337, 8204, 8205
NCBI Taxonomy refs (TaxIDs): 5664,
5666
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There is only one chemically distinct structure:
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