Glycosylphosphatidylinositol synthesi

C. Sutterlin, A. Horvath, P. Gerold, R. T. Schwarz, Y. Wang, M. Dreyfuss H. Riczman. Identification of a species-sjtecific inhibitor of glycosylphosphatidylinositol synthesis. EMBO J, 1997, 16, CNIA-Cm. 

Application to glycosylphosphatidylinositol (CPI) anchor and inositol phosphoglycan (IPG) synthesis... 

From NPOEs to the Synthesis of a Malaria Candidate Glycosylphosphatidylinositol (CPI)... 

Specific proteins can be covalently attached via a carbohydrate bridge to membrane-bound PI (glycosylphosphatidylinositol, or GPI). This allows GPI-anchored proteins rapid lateral mobility on the surface of the plasma membrane. A deficiency in the synthesis of GPI in hematopoietic cells results in a hemolytic disease, paroxysmal nocturnal hemoglobinuria. 

Gillmor, C. S., Lukowitz, W., Brininstool, G., Sedbrook, J. C., Hamann, T., et al., Glycosylphosphatidylinositol-anchored proteins are required for cell wall synthesis and morphogenesis in arabidopsis. Plant Cell 2005, 17 (4), 1128-1140. 

Conrad, R.M., Grogan, M.J., and Bertozzi, C.R., 2002, Stereloselective synthesis of myo-inositol via ring-closing metathesis A building block for glycosylphosphatidylinositol (GPI) anchor synthesis. Org. Lett. 4 1359-1361. 

Glycosylphosphatidylinositol (GPI) membrane anchors constitute a class of glycolipids that covalently link certain proteins to cell and virion surfaces [122,123]. A boost in their chemistry occurred in 1988 when Ferguson et al. reported the first covalent structure of a member of this family [124,125]. The first synthesis of a fully phosphorylated GPI, compound 246 (O Fig. 5), was accomplished by Fraser-Reid s group based entirely on NPG chemistry [126,127,128,129,130]. 

Some examples of research under development include a synthetic conjugated polysaccharide vaccine against Haemophilus influenzae type B, which has been described in 2004 (O Fig. 34). The vaccine prototype was obtained by conjugation to human serum albumin (HSA) [173]. Furthermore, very recently a malaria vaccine has been suggested [174] which is based on the total synthesis of the malaria toxin responsible for the morbidity and mortality associated with malaria. The malaria parasite expresses a large amount of glycosylphosphatidylinositol... 

M. C. Hewitt, D. A. Snyder, and P. H. Seeberger, Rapid synthesis of a glycosylphosphatidylinositol-based malaria vaccine using automated solid-phase oligosaccharide synthesis, /. Am. Chem. Soc., 124 (2002) 13434-13436. 

D. V. Yashunsky, V. S. Borodkin, M. A. J. Ferguson, and A. V. Nikolaev, The chemical synthesis of bioactive glycosylphosphatidylinositols from Trypanosoma cruzi containing an unsaturated fatty acid in the lipid, Angew. Chem. Int. Ed. Engl., 45 (2006) 468—474. 

The synthesis of glycosylphosphatidylinositol (GPI) anchors of proteins, including Thy-1 of neurons and lymphocytes, is primarily carried out within the lumen of the rough endoplasmic reticulum. The anchor consists of a phosphatidylinositol-glucosamine-mannosey-ethanolamine phosphate core that is linked to the a-carboxyl of the carboxyterminal amino acid of a protein (Figure 16-12). This addition takes place within minutes of... 

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