Assembly of a series of malarial glycosylphosphatidylinositol anchor oligosaccharides.
We report an efficient and convergent synthesis of a series of oligosaccharides comprised of the malaria GPI glycan (2a), 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.
Kwon
Yong-Uk
YU
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Soucy
Regina L
RL
Snyder
Daniel A
DA
Seeberger
Peter H
PH
D000818:Animals; D002236:Carbohydrate Conformation; D017261:Glycosylphosphatidylinositols / Q000737:chemistry*; D008358:Mannose / Q000737:chemistry; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000737:chemistry*
D017261:Glycosylphosphatidylinositols; D009844:Oligosaccharides; D008358:Mannose