Synthesis of Galactosylated Glycosylphosphatidylinositol Derivatives from Trypanosoma brucei.

Grube M, Lee BY, Garg M, Michel D, Vilotijević I, Malik A, Seeberger PH, Varón Silva D

Chemistry 24 (13) 3271-3282 [2018-03-02; online 2018-02-01]

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.

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PubMed 29314341

DOI 10.1002/chem.201705511

Crossref 10.1002/chem.201705511