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Assembly of a Series of Malarial Glycosylphosphatidylinositol Anchor Oligosaccharides
Author(s) -
Kwon YongUk,
Soucy Regina L.,
Snyder Daniel A.,
Seeberger Peter H.
Publication year - 2005
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.200400934
Subject(s) - glycan , chemistry , oligosaccharide , glycosylation , biochemistry , moiety , glycosyl , phosphonate , combinatorial chemistry , glycoconjugate , dendrimer , glycolipid , stereochemistry , glycoprotein
We report an efficient and convergent synthesis of a series of oligosaccharides comprised of the malaria GPI glycan ( 2 a ), a promising anti‐malaria vaccine candidate currently in preclinical trials and several related oligosaccharide sequences ( 3 – 8 ) that are possible biosynthetic precursors of the malarial GPI. A flexible synthetic strategy is disclosed that relies on a late‐stage coupling between oligomannosides of varying length and pseudo‐disaccharide glycosyl acceptor 11 to readily access various malarial GPI structures. Phosphorylation was accomplished by mild and efficient H‐phosphonate chemistry before the final deprotection was carried out by using sodium in ammonia. The direct connection of a thiol group via a phosphate diester linkage to the inositol moiety provides a handle for easy conjugation of the GPI glycan to carrier proteins, immobilization on carbohydrate microarrays and photo‐affinity labels identification. These synthetic oligosaccharides will serve as molecular probes.