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Synthesis of Galactosylated Glycosylphosphatidylinositol Derivatives from Trypanosoma brucei
Author(s) -
Grube Maurice,
Lee BoYoung,
Garg Monika,
Michel Dana,
Vilotijević Ivan,
Malik Ankita,
Seeberger Peter H.,
Varón Silva Daniel
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201705511
Subject(s) - trypanosoma brucei , glycolipid , biology , epitope , glycoprotein , immune system , trypanosoma , antigen , microbiology and biotechnology , biochemistry , immunology , virology , gene
Trypanosoma brucei uses variant surface glycoproteins (VSGs) to evade the host immune system and ensure parasitic longevity in animals and humans. VSGs are attached to the cell membrane by complex glycosylphosphatidylinositol anchors (GPI). Distinguishing structural feature of VSG GPIs are multiple α‐ and β‐galactosides attached to the conserved GPI core structure. T. brucei GPIs have been associated with macrophage activation and alleviation of parasitemia during infection, acting as disease onset delaying antigens. Literature reports that link structural modifications in the GPIs to changes in biological activity are contradictory. We have established a synthetic route to prepare structurally overlapping GPI derivatives bearing different T. brucei characteristic structural modifications. The GPI collection will be used to assess the effect of galactosylation and phosphorylation on T. brucei GPI immunomodulatory activity, and to perform an epitope mapping of this complex glycolipid as potential diagnostic marker for Trypanosomiasis. A strategy for the synthesis of a complete α‐tetragalactoside using the 2‐naphthylmethyl protecting group and for subsequent attachment of GPI fragments to peptides is presented.