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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Protozoan Parasites Glycosylphosphatidylinositol Anchors: Structures, Functions and Trends for Drug Discovery

Author(s): Ana Luísa Malaco Morotti, Maristela Braga Martins-Teixeira and Ivone Carvalho*

Volume 26 , Issue 23 , 2019

Page: [4301 - 4322] Pages: 22

DOI: 10.2174/0929867324666170727110801

Price: $65


Background: Glycosylphosphatidylinositol (GPI) anchors are molecules located on cell membranes of all eukaryotic organisms. Proteins, enzymes, and other macromolecules which are anchored by GPIs are essential elements for interaction between cells, and are widely used by protozoan parasites when compared to higher eukaryotes.

Methods: More than one hundred references were collected to obtain broad information about mammalian and protozoan parasites’ GPI structures, biosynthetic pathways, functions and attempts to use these molecules as drug targets against parasitic diseases. Differences between GPI among species were compared and highlighted. Strategies for drug discovery and development against protozoan GPI anchors were discussed based on what has been reported on literature.

Results: There are many evidences that GPI anchors are crucial for parasite’s survival and interaction with hosts’ cells. Despite all GPI anchors contain a conserved glycan core, they present variations regarding structural features and biosynthetic pathways between organisms, which could offer adequate selectivity to validate GPI anchors as drug targets. Discussion was developed with focus on the following parasites: Trypanosoma brucei, Trypanosoma cruzi, Leishmania, Plasmodium falciparum and Toxoplasma gondii, causative agents of tropical neglected diseases.

Conclusion: This review debates the main variances between parasitic and mammalian GPI anchor biosynthesis and structures, as well as clues for strategic development for new anti-parasitic therapies based on GPI anchors.

Keywords: Glycosylphosphatidylinositol (GPI), phosphatidylinositol, protozoan, lipopeptidophosphoglycans (LPPGs), drug discovery, immunotherapy.

McConville, M.J.; Ferguson, M.A.J. The structure, biosynthesis and function of glycosylated phosphatidylinositols in the parasitic protozoa and higher eukaryotes. Biochem. J., 1993, 294(Pt 2), 305-324.
[] [PMID: 8373346]
de Macedo, C.S.; Shams-Eldin, H.; Smith, T.K.; Schwarz, R.T.; Azzouz, N. Inhibitors of glycosyl-phosphatidylinositol anchor biosynthesis. Biochimie, 2003, 85(3-4), 465-472.
[] [PMID: 12770785]
Mendonca-Previato, L.; Todeschini, A.R.; Heise, N.; Agrellos, O.A.; Dias, W.B.; Previato, J.O. Chemical structure of major glycoconjugates from parasites. Curr. Org. Chem., 2008, 12(11), 926-939.
Ferguson, M.A.J. The surface glycoconjugates of trypanosomatid parasites. Philos. Trans. R. Soc. Lond. B Biol. Sci., 1997, 352(1359), 1295-1302.
[] [PMID: 9355120]
Tsai, Y.H.; Liu, X.; Seeberger, P.H. Chemical biology of glycosylphosphatidylinositol anchors. Angew. Chem. Int. Ed. Engl., 2012, 51(46), 11438-11456.
[] [PMID: 23086912]
Chawla, B.; Madhubala, R. Drug targets in Leishmania. J. Parasit. Dis., 2010, 34(1), 1-13.
[] [PMID: 21526026]
Tsai, Y.H.; Grube, M.; Seeberger, P.H.; Silva, D.V. Glycosylphosphatidylinositols of protozoan parasites. Trends Glycosci. Glycotechnol., 2012, 24(140), 231-243.
Blum, M.L.; Down, J.A.; Gurnett, A.M.; Carrington, M.; Turner, M.J.; Wiley, D.C. A structural motif in the variant surface glycoproteins of Trypanosoma brucei. Nature, 1993, 362(6421), 603-609.
[] [PMID: 8464512]
Sukhareva-Buell, N.N. Biologically Active Substances of Protozoa; Springer Science+Business Media Dordrecht B. V.: Netherlands, 2003, pp. 46-54.
Roberts, D.D.; Olson, L.D.; Barile, M.F.; Ginsburg, V.; Krivan, H.C. Sialic acid-dependent adhesion of Mycoplasma pneumoniae to purified glycoproteins. J. Biol. Chem., 1989, 264(16), 9289-9293.
[PMID: 2470754]
Luhrs, C.A.; Slomiany, B.L. A human membrane-associated folate binding protein is anchored by a glycosyl-phosphatidylinositol tail. J. Biol. Chem., 1989, 264(36), 21446-21449.
[PMID: 2557328]
Walter, E.I.; Roberts, W.L.; Rosenberry, T.L.; Ratnoff, W.D.; Medof, M.E. Structural basis for variations in the sensitivity of human decay accelerating factor to phosphatidylinositol-specific phospholipase C cleavage. J. Immunol., 1990, 144(3), 1030-1036.
[PMID: 1688588]
Lee, H.C.; Shoda, R.; Krall, J.A.; Foster, J.D.; Selhub, J.; Rosenberry, T.L. Folate binding protein from kidney brush border membranes contains components characteristic of a glycoinositol phospholipid anchor. Biochemistry, 1992, 31(12), 3236-3243.
[] [PMID: 1372826]
Cardoso, M.S.; Junqueira, C.; Trigueiro, R.C.; Shams-Eldin, H.; Macedo, C.S.; Araújo, P.R.; Gomes, D.A.; Martinelli, P.M.; Kimmel, J.; Stahl, P.; Niehus, S.; Schwarz, R.T.; Previato, J.O.; Mendonça-Previato, L.; Gazzinelli, R.T.; Teixeira, S.M.R. Identification and functional analysis of Trypanosoma cruzi genes that encode proteins of the glycosylphosphatidylinositol biosynthetic pathway. PLoS Negl. Trop. Dis., 2013, 7(8)e2369
[] [PMID: 23951384]
Conzelmann, A.; Puoti, A.; Lester, R.L.; Desponds, C. Two different types of lipid moieties are present in glycophosphoinositol-anchored membrane proteins of Saccharomyces cerevisiae. EMBO J., 1992, 11(2), 457-466.
[] [PMID: 1531630]
Fankhauser, C.; Homans, S.W.; Thomas-Oates, J.E.; McConville, M.J.; Desponds, C.; Conzelmann, A.; Ferguson, M.A.J. Structures of glycosylphosphatidylinositol membrane anchors from Saccharomyces cerevisiae. J. Biol. Chem., 1993, 268(35), 26365-26374.
[PMID: 8253761]
Eckert, V.; Gerold, P.; Schwarz, R.T. In Glycosciences: status and perspectives; Gabius, H.-J.; Gabius, S., Eds.; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim,, 2002, pp. 223-243.
Almeida, I.C.; Gazzinelli, R.; Ferguson, M.A.J.; Travassos, L.R. Trypanosoma cruzi mucins: potential functions of a complex structure. Mem. Inst. Oswaldo Cruz, 1999, 94(I)(Suppl. 1), 173-176.
[] [PMID: 10677709]
Mucci; Juan; Lantos; B., A.; Buscaglia; A., C.; Leguizamón; Susana, M.; Campetella; Oscar. The Trypanosoma cruzi surface, a nanoscale patchwork quilt the Trypanosoma cruzi surface, a nanoscale patchwork quilt. Trends Parasitol., 2016. in press
Serrano, A.A.; Schenkman, S.; Yoshida, N.; Mehlert, A.; Richardson, J.M.; Ferguson, M.A.J. The lipid structure of the glycosylphosphatidylinositol-anchored mucin-like sialic acid acceptors of Trypanosoma cruzi changes during parasite differentiation from epimastigotes to infective metacyclic trypomastigote forms. J. Biol. Chem., 1995, 270(45), 27244-27253.
[] [PMID: 7592983]
Olivier, M.; Atayde, V.D.; Isnard, A.; Hassani, K.; Shio, M.T. Leishmania virulence factors: focus on the metalloprotease GP63. Microbes Infect., 2012, 14(15), 1377-1389.
[] [PMID: 22683718]
Novozhilova, N.M.; Bovin, N.V. Structure, functions, and biosynthesis of glycoconjugates of Leishmania spp. cell surface. Biochemistry (Mosc.), 2010, 75(6), 686-694.
[] [PMID: 20636259]
Cabezas, Y.; Legentil, L.; Robert-Gangneux, F.; Daligault, F.; Belaz, S.; Nugier-Chauvin, C.; Tranchimand, S.; Tellier, C.; Gangneux, J.P.; Ferrières, V. Leishmania cell wall as a potent target for antiparasitic drugs. A focus on the glycoconjugates. Org. Biomol. Chem., 2015, 13(31), 8393-8404.
[] [PMID: 26130402]
Naik, R.S.; Davidson, E.A.; Gowda, D.C. Developmental stage-specific biosynthesis of glycosylphosphatidylinositol anchors in intraerythrocytic Plasmodium falciparum and its inhibition in a novel manner by mannosamine. J. Biol. Chem., 2000, 275(32), 24506-24511.
[] [PMID: 10833517]
Naik, R.S.; Krishnegowda, G.; Gowda, D.C. Glucosamine inhibits inositol acylation of the glycosylphosphatidylinositol anchors in intraerythrocytic Plasmodium falciparum. J. Biol. Chem., 2003, 278(3), 2036-2042.
[] [PMID: 12419814]
Pekari, K.; Tailler, D.; Weingart, R.; Schmidt, R.R. Synthesis of the fully phosphorylated GPI anchor pseudohexasaccharide of Toxoplasma gondii. J. Org. Chem., 2001, 66(22), 7432-7442.
[] [PMID: 11681958]
Niehus, S.; Smith, T.K.; Azzouz, N.; Campos, M.A.; Dubremetz, J.F.; Gazzinelli, R.T.; Schwarz, R.T.; Debierre-Grockiego, F. Virulent and avirulent strains of Toxoplasma gondii which differ in their glycosylphosphatidylinositol content induce similar biological functions in macrophages. PLoS One, 2014, 9(1)e85386
[] [PMID: 24489660]
Wichroski, M.J.; Ward, G.E. Biosynthesis of glycosylphosphatidylinositol is essential to the survival of the protozoan parasite Toxoplasma gondii. Eukaryot. Cell, 2003, 2(5), 1132-1136.
[] [PMID: 14555496]
Smith, T.K.; Kimmel, J.; Azzouz, N.; Shams-Eldin, H.; Schwarz, R.T. The role of inositol acylation and inositol deacylation in the Toxoplasma gondii glycosylphosphatidylinositol biosynthetic pathway. J. Biol. Chem., 2007, 282(44), 32032-32042.
[] [PMID: 17804418]
Doering, T.L.; Masterson, W.J.; Englund, P.T.; Hart, G.W. Biosynthesis of the glycosyl phosphatidylinositol membrane anchor of the trypanosome variant surface glycoprotein. Origin of the non-acetylated glucosamine. J. Biol. Chem., 1989, 264(19), 11168-11173.
[PMID: 2525555]
Masterson, W.J.; Doering, T.L.; Hart, G.W.; Englund, P.T. A novel pathway for glycan assembly: biosynthesis of the glycosyl-phosphatidylinositol anchor of the trypanosome variant surface glycoprotein. Cell, 1989, 56(5), 793-800.
[] [PMID: 2924349]
Menon, A.K.; Mayor, S.; Schwarz, R.T. Biosynthesis of glycosyl-phosphatidylinositol lipids in Trypanosoma brucei: involvement of mannosyl-phosphoryldolichol as the mannose donor. EMBO J., 1990, 9(13), 4249-4258.
[] [PMID: 2148289]
Menon, A.K.; Eppinger, M.; Mayor, S.; Schwarz, R.T. Phosphatidylethanolamine is the donor of the terminal phosphoethanolamine group in trypanosome glycosylphosphatidylinositols. EMBO J., 1993, 12(5), 1907-1914.
[] [PMID: 8491183]
Bangs, J.D.; Hereld, D.; Krakow, J.L.; Hart, G.W.; Englund, P.T. Rapid processing of the carboxyl terminus of a trypanosome variant surface glycoprotein. Proc. Natl. Acad. Sci. USA, 1985, 82(10), 3207-3211.
[] [PMID: 3858818]
Ferguson, M.A.J.; Duszenko, M.; Lamont, G.S.; Overath, P.; Cross, G.A.M. Biosynthesis of Trypanosoma brucei variant surface glycoproteins. N-glycosylation and addition of a phosphatidylinositol membrane anchor. J. Biol. Chem., 1986, 261(1), 356-362.
[PMID: 2934386]
Doering, T.L.; Masterson, W.J.; Hart, G.W.; Englund, P.T. Biosynthesis of glycosyl phosphatidylinositol membrane anchors. J. Biol. Chem., 1990, 265(2), 611-614.
[PMID: 2136848]
Masterson, W.J.; Raper, J.; Doering, T.L.; Hart, G.W.; Englund, P.T. Fatty acid remodeling: a novel reaction sequence in the biosynthesis of trypanosome glycosyl phosphatidylinositol membrane anchors. Cell, 1990, 62(1), 73-80.
[] [PMID: 1694728]
Menon, A.K.; Schwarz, R.T.; Mayor, S.; Cross, G.A.M. Cell-free synthesis of glycosyl-phosphatidylinositol precursors for the glycolipid membrane anchor of Trypanosoma brucei variant surface glycoproteins. Structural characterization of putative biosynthetic intermediates. J. Biol. Chem., 1990, 265(16), 9033-9042.
[PMID: 1693147]
Menon, A.K. Biosynthesis of glycosyl-phosphatidylinositol. Cell Biol. Int. Rep., 1991, 15(11), 1007-1021.
[] [PMID: 1838300]
Nagamune, K.; Nozaki, T.; Maeda, Y.; Ohishi, K.; Fukuma, T.; Hara, T.; Schwarz, R.T.; Sutterlin, C.; Brun, R.; Riezman, H.; Kinoshita, T. Critical roles of glycosylphosphatidylinositol for Trypanosoma brucei. Proc. Natl. Acad. Sci. USA, 2000, 97(19), 10336-10341.
[] [PMID: 10954751]
Chang, T.; Milne, K.G.; Güther, M.L.S.; Smith, T.K.; Ferguson, M.A.J. Cloning of Trypanosoma brucei and Leishmania major genes encoding the GlcNAc-phosphatidylinositol de-N-acetylase of glycosylphosphatidylinositol biosynthesis that is essential to the African sleeping sickness parasite. J. Biol. Chem., 2002, 277(51), 50176-50182.
[] [PMID: 12364327]
Ralton, J.E.; McConville, M.J. Delineation of three pathways of glycosylphosphatidylinositol biosynthesis in Leishmania mexicana. Precursors from different pathways are assembled on distinct pools of phosphatidylinositol and undergo fatty acid remodeling. J. Biol. Chem., 1998, 273(7), 4245-4257.
[] [PMID: 9461623]
Smith, T.K.; Sharma, D.K.; Crossman, A.; Brimacombe, J.S.; Ferguson, M.A.J. Selective inhibitors of the glycosylphosphatidylinositol biosynthetic pathway of Trypanosoma brucei. EMBO J., 1999, 18(21), 5922-5930.
[] [PMID: 10545104]
Smith, T.K.; Crossman, A.; Borissow, C.N.; Paterson, M.J.; Dix, A.; Brimacombe, J.S.; Ferguson, M.A.J. Specificity of GlcNAc-PI de-N-acetylase of GPI biosynthesis and synthesis of parasite-specific suicide substrate inhibitors. EMBO J., 2001, 20(13), 3322-3332.
[] [PMID: 11432820]
Ferguson, M.A.J. The structure, biosynthesis and functions of glycosylphosphatidylinositol anchors, and the contributions of trypanosome research. J. Cell Sci., 1999, 112(Pt 17), 2799-2809.
[PMID: 10444375]
Smith, T.K.; Milne, F.C.; Sharma, D.K.; Crossman, A.; Brimacombe, J.S.; Ferguson, M.A.J. Early steps in glycosylphosphatidylinositol biosynthesis in Leishmania major. Biochem. J., 1997, 326(Pt 2), 393-400.
[] [PMID: 9291110]
Milne, K.G.; Ferguson, M.A.J.; Masterson, W.J. Inhibition of the GlcNAc transferase of the glycosylphosphatidylinositol anchor biosynthesis in African trypanosomes. Eur. J. Biochem., 1992, 208(2), 309-314.
[] [PMID: 1325903]
Smith, T.K.; Crossman, A.; Brimacombe, J.S.; Ferguson, M.A.J. Chemical validation of GPI biosynthesis as a drug target against African sleeping sickness. EMBO J., 2004, 23(23), 4701-4708.
[] [PMID: 15526036]
Koeller, C.M.; Heise, N. The sphingolipid biosynthetic pathway is a potential target for chemotherapy against Chagas disease. Enzyme Research, 2011, 2011(ID 648159), 1-13.
Sharma, D.K.; Smith, T.K.; Weller, C.T.; Crossman, A.; Brimacombe, J.S.; Ferguson, M.A.J. Differences between the trypanosomal and human GlcNAc-PI de-N-acetylases of glycosylphosphatidylinositol membrane anchor biosynthesis. Glycobiology, 1999, 9(4), 415-422.
[] [PMID: 10089216]
Milne, K.G.; Field, R.A.; Masterson, W.J.; Cottaz, S.; Brimacombe, J.S.; Ferguson, M.A.J. Partial purification and characterization of the N-acetylglucosaminyl-phosphatidylinositol de-N-acetylase of glycosylphosphatidylinositol anchor biosynthesis in African trypanosomes. J. Biol. Chem., 1994, 269(23), 16403-16408.
[PMID: 8206949]
Sharma, D.K.; Smith, T.K.; Crossman, A.; Brimacombe, J.S.; Ferguson, M.A.J. Substrate specificity of the N-acetylglucosaminyl-phosphatidylinositol de-N-acetylase of glycosylphosphatidylinositol membrane anchor biosynthesis in African trypanosomes and human cells. Biochem. J., 1997, 328(Pt 1), 171-177.
[] [PMID: 9359849]
Smith, T.K.; Paterson, M.J.; Crossman, A.; Brimacombe, J.S.; Ferguson, M.A.J. Parasite-specific inhibition of the glycosylphosphatidylinositol biosynthetic pathway by stereoisomeric substrate analogues. Biochemistry, 2000, 39(38), 11801-11807.
[] [PMID: 10995248]
Capes, A.S.; Crossman, A.; Urbaniak, M.D.; Gilbert, S.H.; Ferguson, M.A.J.; Gilbert, I.H. Probing the substrate specificity of Trypanosoma brucei GlcNAc-PI de-N-acetylase with synthetic substrate analogues. Org. Biomol. Chem., 2014, 12(12), 1919-1934.
[] [PMID: 24519084]
Crossman, A.T.; Urbaniak, M.D.; Ferguson, M.A.J. Synthesis of 1-D-6-O-[2-(N-hydroxyaminocarbonyl)amino-2-deoxy-alpha-D-glucopyranosyl]-myo-inositol 1-(n-octadecyl phosphate): a potential metalloenzyme inhibitor of glycosylphosphatidylinositol biosynthesis. Carbohydr. Res., 2008, 343(9), 1478-1481.
[] [PMID: 18479678]
Parrish, D.A.; Zou, Z.; Allen, C.L.; Day, C.S.; King, S.B. A convenient method for the synthesis of N-hydroxyureas. Tetrahedron Lett., 2005, 46(51), 8841-8843.
Abdelwahab, N.Z.; Crossman, A.T.; Sullivan, L.; Ferguson, M.A.J.; Urbaniak, M.D. Inhibitors incorporating zinc-binding groups target the GlcNAc-PI de-N-acetylase in Trypanosoma brucei, the causative agent of African sleeping sickness. Chem. Biol. Drug Des., 2012, 79(3), 270-278.
[] [PMID: 22222041]
Almani, P.G.N.; Sharifi, I.; Kazemi, B.; Babaei, Z.; Bandehpour, M.; Salari, S.; Dezaki, E.S.; Tohidi, F.; Mohammadi, M.A. The role of GlcNAc-PI-de-N-acetylase gene by gene knockout through homologous recombination and its consequences on survival, growth and infectivity of Leishmania major in in vitro and in vivo conditions. Acta Trop., 2016, 154, 63-72.
[] [PMID: 26571069]
Singh, S.; Mandlik, V.; Shinde, S. Molecular dynamics simulations and statistical coupling analysis of GPI12 in L. major: functional co-evolution and conservedness reveals potential drug-target sites. Mol. Biosyst., 2015, 11(3), 958-968.
[] [PMID: 25609494]
Rashmi, M.; Swati, D. In silico drug re-purposing against African sleeping sickness using GlcNAc-PI de-N-acetylase as an experimental target. Comput. Biol. Chem., 2015, 59(Pt A), 87-94.
[] [PMID: 26476127]
Tsukahara, K.; Hata, K.; Nakamoto, K.; Sagane, K.; Watanabe, N.A.; Kuromitsu, J.; Kai, J.; Tsuchiya, M.; Ohba, F.; Jigami, Y.; Yoshimatsu, K.; Nagasu, T. Medicinal genetics approach towards identifying the molecular target of a novel inhibitor of fungal cell wall assembly. Mol. Microbiol., 2003, 48(4), 1029-1042.
[] [PMID: 12753194]
Umemura, M.; Okamoto, M.; Nakayama, K.; Sagane, K.; Tsukahara, K.; Hata, K.; Jigami, Y. GWT1 gene is required for inositol acylation of glycosylphosphatidylinositol anchors in yeast. J. Biol. Chem., 2003, 278(26), 23639-23647.
[] [PMID: 12714589]
McLellan, C.A.; Whitesell, L.; King, O.D.; Lancaster, A.K.; Mazitschek, R.; Lindquist, S. Inhibiting GPI anchor biosynthesis in fungi stresses the endoplasmic reticulum and enhances immunogenicity. ACS Chem. Biol., 2012, 7(9), 1520-1528.
[] [PMID: 22724584]
Hata, K.; Horii, T.; Miyazaki, M.; Watanabe, N.A.; Okubo, M.; Sonoda, J.; Nakamoto, K.; Tanaka, K.; Shirotori, S.; Murai, N.; Inoue, S.; Matsukura, M.; Abe, S.; Yoshimatsu, K.; Asada, M. Efficacy of oral E1210, a new broad-spectrum antifungal with a novel mechanism of action, in murine models of candidiasis, aspergillosis, and fusariosis. Antimicrob. Agents Chemother., 2011, 55(10), 4543-4551.
[] [PMID: 21788462]
Murakami, Y.; Siripanyapinyo, U.; Hong, Y.; Kang, J.Y.; Ishihara, S.; Nakakuma, H.; Maeda, Y.; Kinoshita, T. PIG-W is critical for inositol acylation but not for flipping of glycosylphosphatidylinositol-anchor. Mol. Biol. Cell, 2003, 14(10), 4285-4295.
[] [PMID: 14517336]
Hilley, J.D.; Zawadzki, J.L.; McConville, M.J.; Coombs, G.H.; Mottram, J.C. Leishmania mexicana mutants lacking glycosylphosphatidylinositol (GPI):protein transamidase provide insights into the biosynthesis and functions of GPI-anchored proteins. Mol. Biol. Cell, 2000, 11(4), 1183-1195.
[] [PMID: 10749923]
Shinde, S.; Mol, M.; Jamdar, V.; Singh, S. Molecular modeling and molecular dynamics simulations of GPI 14 in Leishmania major: insight into the catalytic site for active site directed drug design. J. Theor. Biol., 2014, 351, 37-46.
[] [PMID: 24583312]
Naderer, T.; McConville, M.J. Characterization of a Leishmania mexicana mutant defective in synthesis of free and protein-linked GPI glycolipids. Mol. Biochem. Parasitol., 2002, 125(1-2), 147-161.
[] [PMID: 12467982]
Field, M.C.; Medina-Acosta, E.; Cross, G.A.M. Inhibition of glycosylphosphatidylinositol biosynthesis in Leishmania mexicana by mannosamine. J. Biol. Chem., 1993, 268(13), 9570-9577.
[PMID: 8387500]
Urbaniak, M.D.; Yashunsky, D.V.; Crossman, A.; Nikolaev, A.V.; Ferguson, M.A.J. Probing enzymes late in the trypanosomal glycosylphosphatidylinositol biosynthetic pathway with synthetic glycosylphosphatidylinositol analogues. ACS Chem. Biol., 2008, 3(10), 625-634.
[] [PMID: 18928250]
Brown, J.R.; Güther, M.L.S.; Field, R.A.; Ferguson, M.A.J. Hydrophobic mannosides act as acceptors for trypanosome alpha-mannosyltransferases. Glycobiology, 1997, 7(4), 549-558.
[] [PMID: 9184836]
Sütterlin, C.; Horvath, A.; Gerold, P.; Schwarz, R.T.; Wang, Y.; Dreyfuss, M.; Riezman, H. Identification of a species-specific inhibitor of glycosylphosphatidylinositol synthesis. EMBO J., 1997, 16(21), 6374-6383.
[] [PMID: 9351820]
Hong, Y.; Maeda, Y.; Watanabe, R.; Ohishi, K.; Mishkind, M.; Riezman, H.; Kinoshita, T. Pig-n, a mammalian homologue of yeast Mcd4p, is involved in transferring phosphoethanolamine to the first mannose of the glycosylphosphatidylinositol. J. Biol. Chem., 1999, 274(49), 35099-35106.
[] [PMID: 10574991]
Smith, T.K.; Gerold, P.; Crossman, A.; Paterson, M.J.; Borissow, C.N.; Brimacombe, J.S.; Ferguson, M.A.J.; Schwarz, R.T. Substrate specificity of the Plasmodium falciparum glycosylphosphatidylinositol biosynthetic pathway and inhibition by species-specific suicide substrates. Biochemistry, 2002, 41(41), 12395-12406.
[] [PMID: 12369829]
Chandra, S.; Ruhela, D.; Deb, A.; Vishwakarma, R.A. Glycobiology of the Leishmania parasite and emerging targets for antileishmanial drug discovery. Expert Opin. Ther. Targets, 2010, 14(7), 739-757.
[] [PMID: 20536412]
Hong, Y.; Kinoshita, T. Trypanosome glycosylphosphatidylinositol biosynthesis. Korean J. Parasitol., 2009, 47(3), 197-204.
[] [PMID: 19724691]
Doering, T.L.; Raper, J.; Buxbaum, L.U.; Adams, S.P.; Gordon, J.I.; Hart, G.W.; Englund, P.T. An analog of myristic acid with selective toxicity for African trypanosomes. Science, 1991, 252(5014), 1851-1854.
[] [PMID: 1829548]
Mensa-Wilmot, K.; LeBowitz, J.H.; Chang, K.P.; al-Qahtani, A.; McGwire, B.S.; Tucker, S.; Morris, J.C.; Glycosylphosphatidylinositol, A. A glycosylphosphatidylinositol (GPI)-negative phenotype produced in Leishmania major by GPI phospholipase C from Trypanosoma brucei: topography of two GPI pathways. J. Cell Biol., 1994, 124(6), 935-947.
[] [PMID: 8132715]
Garg, N.; Postan, M.; Mensa-Wilmot, K.; Tarleton, R.L. Glycosylphosphatidylinositols are required for the development of Trypanosoma cruzi amastigotes. Infect. Immun., 1997, 65(10), 4055-4060.
[PMID: 9317007]
Zheng, Z.; Tweten, R.K.; Mensa-Wilmot, K. Intracellular glycosylphosphatidylinositols accumulate on endosomes: toxicity of alpha-toxin to Leishmania major. Eukaryot. Cell, 2005, 4(3), 556-566.
[] [PMID: 15755918]
Takami, N.; Oda, K.; Ikehara, Y. Aberrant processing of alkaline phosphatase precursor caused by blocking the synthesis of glycosylphosphatidylinositol. J. Biol. Chem., 1992, 267(2), 1042-1047.
[PMID: 1530933]
Santos de Macedo, C.; Gerold, P.; Jung, N.; Azzouz, N.; Kimmel, J.; Schwarz, R.T. Inhibition of glycosyl-phosphatidylinositol biosynthesis in Plasmodium falciparum by C-2 substituted mannose analogues. Eur. J. Biochem., 2001, 268(23), 6221-6228.
[] [PMID: 11733018]
Banerjee, D.K. Amphomycin inhibits mannosylphosphoryldolichol synthesis by forming a complex with dolichylmonophosphate. J. Biol. Chem., 1989, 264(4), 2024-2028.
[PMID: 2464586]
Prado-Figueroa, M.; Raper, J.; Opperdoes, F.R. Possible localisation of dolichol-dependent mannosyltransferase of Trypanosoma brucei to the rough endoplasmic reticulum. Mol. Biochem. Parasitol., 1994, 63(2), 255-264.
[] [PMID: 7516492]
Ilgoutz, S.C.; Zawadzki, J.L.; Ralton, J.E.; McConville, M.J. Evidence that free GPI glycolipids are essential for growth of Leishmania mexicana. EMBO J., 1999, 18(10), 2746-2755.
[] [PMID: 10329621]
González-Bulnes, P.; Bobenchik, A.M.; Augagneur, Y.; Cerdan, R.; Vial, H.J.; Llebaria, A.; Ben Mamoun, C. PG12, a phospholipid analog with potent antimalarial activity, inhibits Plasmodium falciparum CTP: phosphocholine cytidylyltransferase activity. J. Biol. Chem., 2011, 286(33), 28940-28947.
[] [PMID: 21705805]
Ancelin, M.L.; Calas, M.; Vidal-Sailhan, V.; Herbuté, S.; Ringwald, P.; Vial, H.J. Potent inhibitors of Plasmodium phospholipid metabolism with a broad spectrum of in vitro antimalarial activities. Antimicrob. Agents Chemother., 2003, 47(8), 2590-2597.
[] [PMID: 12878524]
Wein, S.; Maynadier, M.; Bordat, Y.; Perez, J.; Maheshwari, S.; Bette-Bobillo, P.; Tran Van Ba, C.; Penarete-Vargas, D.; Fraisse, L.; Cerdan, R.; Vial, H. Transport and pharmacodynamics of albitiazolium, an antimalarial drug candidate. Br. J. Pharmacol., 2012, 166(8), 2263-2276.
[] [PMID: 22471905]
Calas, M.; Ancelin, M.L.; Cordina, G.; Portefaix, P.; Piquet, G.; Vidal-Sailhan, V.; Vial, H. Antimalarial activity of compounds interfering with Plasmodium falciparum phospholipid metabolism: Comparison between mono- and bisquaternary ammonium salts. J. Med. Chem., 2000, 43(3), 505-516.
[] [PMID: 10669577]
Wengelnik, K.; Vidal, V.; Ancelin, M.L.; Cathiard, A.M.; Morgat, J.L.; Kocken, C.H.; Calas, M.; Herrera, S.; Thomas, A.W.; Vial, H.J. A class of potent antimalarials and their specific accumulation in infected erythrocytes. Science, 2002, 295(5558), 1311-1314.
[] [PMID: 11847346]
Ibrahim, H.M.S.; Al-Salabi, M.I.; El Sabbagh, N.; Quashie, N.B.; Alkhaldi, A.A.M.; Escale, R.; Smith, T.K.; Vial, H.J.; de Koning, H.P. Symmetrical choline-derived dications display strong anti-kinetoplastid activity. J. Antimicrob. Chemother., 2011, 66(1), 111-125.
[] [PMID: 21078603]
Ramakrishnan, S.; Serricchio, M.; Striepen, B.; Bütikofer, P. Lipid synthesis in protozoan parasites: A comparison between kinetoplastids and apicomplexans. Prog. Lipid Res., 2013, 52(4), 488-512.
[] [PMID: 23827884]
Jiménez-López, J.M.; Carrasco, M.P.; Segovia, J.L.; Marco, C. Hexadecylphosphocholine inhibits phosphatidylcholine synthesis via both the methylation of phosphatidylethanolamine and CDP-choline pathways in HepG2 cells. Int. J. Biochem. Cell Biol., 2004, 36(1), 153-161.
[] [PMID: 14592540]
Jones, S.M.; Urch, J.E.; Brun, R.; Harwood, J.L.; Berry, C.; Gilbert, I.H. Analogues of thiolactomycin as potential anti-malarial and anti-trypanosomal agents. Bioorg. Med. Chem., 2004, 12(4), 683-692.
[] [PMID: 14759729]
Jones, S.M.; Urch, J.E.; Kaiser, M.; Brun, R.; Harwood, J.L.; Berry, C.; Gilbert, I.H. Analogues of thiolactomycin as potential antimalarial agents. J. Med. Chem., 2005, 48(19), 5932-5941.
[] [PMID: 16161997]
Lear, M.J.; Reux, B.; Sekar, K. GPI Membrane Anchors-The Much Needed Link; Dangerfield, J.A., Ed.; Bentham Science Publishers Ltd., 2010, pp. 64-82.
Nikolaev, A.V.; Al-Maharik, N. Synthetic glycosylphosphatidylinositol (GPI) anchors: How these complex molecules have been made. Nat. Prod. Rep., 2011, 28(5), 970-1020.
[] [PMID: 21448495]
Yu, S.; Guo, Z.; Johnson, C.; Gu, G.; Wu, Q. Recent progress in synthetic and biological studies of GPI anchors and GPI-anchored proteins. Curr. Opin. Chem. Biol., 2013, 17(6), 1006-1013.
[] [PMID: 24128440]
Boutlis, C.S.; Gowda, D.C.; Naik, R.S.; Maguire, G.P.; Mgone, C.S.; Bockarie, M.J.; Lagog, M.; Ibam, E.; Lorry, K.; Anstey, N.M. Antibodies to Plasmodium falciparum glycosylphosphatidylinositols: inverse association with tolerance of parasitemia in Papua New Guinean children and adults. Infect. Immun., 2002, 70(9), 5052-5057.
[] [PMID: 12183552]
Boutlis, C.S.; Fagan, P.K.; Gowda, D.C.; Lagog, M.; Mgone, C.S.; Bockarie, M.J.; Anstey, N.M.; Immunoglobulin, G.; Immunoglobulin, G. IgG) responses to Plasmodium falciparum glycosylphosphatidylinositols are short-lived and predominantly of the IgG3 subclass. J. Infect. Dis., 2003, 187(5), 862-865.
[] [PMID: 12599061]
Suguitan, A.L., Jr; Gowda, D.C.; Fouda, G.; Thuita, L.; Zhou, A.; Djokam, R.; Metenou, S.; Leke, R.G.F.; Taylor, D.W. Lack of an association between antibodies to Plasmodium falciparum glycosylphosphatidylinositols and malaria-associated placental changes in Cameroonian women with preterm and full-term deliveries. Infect. Immun., 2004, 72(9), 5267-5273.
[] [PMID: 15322022]
Perraut, R.; Diatta, B.; Marrama, L.; Garraud, O.; Jambou, R.; Longacre, S.; Krishnegowda, G.; Dieye, A.; Gowda, D.C. Differential antibody responses to Plasmodium falciparum glycosylphosphatidylinositol anchors in patients with cerebral and mild malaria. Microbes Infect., 2005, 7(4), 682-687.
[] [PMID: 15848275]
Naik, R.S.; Krishnegowda, G.; Ockenhouse, C.F.; Gowda, D.C. Naturally elicited antibodies to glycosylphosphatidylinositols (GPIs) of Plasmodium falciparum require intact GPI structures for binding and are directed primarily against the conserved glycan moiety. Infect. Immun., 2006, 74(2), 1412-1415.
[] [PMID: 16428795]
Schofield, L.; Hewitt, M.C.; Evans, K.; Siomos, M.A.; Seeberger, P.H. Synthetic GPI as a candidate anti-toxic vaccine in a model of malaria. Nature, 2002, 418(6899), 785-789.
[] [PMID: 12181569]
Kedzierski, L. Leishmaniasis vaccine: where are we today? J. Glob. Infect. Dis., 2010, 2(2), 177-185.
[] [PMID: 20606974]
Russo, D.M.; Burns, J.M., Jr; Carvalho, E.M.; Armitage, R.J.; Grabstein, K.H.; Button, L.L.; McMaster, W.R.; Reed, S.G. Human T cell responses to gp63, a surface antigen of Leishmania. J. Immunol., 1991, 147(10), 3575-3580.
[PMID: 1940356]
Sjölander, A.; Baldwin, T.M.; Curtis, J.M.; Bengtsson, K.L.; Handman, E. Vaccination with recombinant Parasite Surface Antigen 2 from Leishmania major induces a Th1 type of immune response but does not protect against infection. Vaccine, 1998, 16(20), 2077-2084.
[] [PMID: 9796067]
Forestier, C.L.; Gao, Q.; Boons, G.J. Leishmania lipophosphoglycan: how to establish structure-activity relationships for this highly complex and multifunctional glycoconjugate? Front. Cell. Infect. Microbiol., 2015, 4, 193.
[] [PMID: 25653924]
McConville, M.J.; Bacic, A.; Mitchell, G.F.; Handman, E. Lipophosphoglycan of Leishmania major that vaccinates against cutaneous leishmaniasis contains an alkylglycerophosphoinositol lipid anchor. Proc. Natl. Acad. Sci. USA, 1987, 84(24), 8941-8945.
[] [PMID: 3480520]
Nyame, A.K.; Kawar, Z.S.; Cummings, R.D. Antigenic glycans in parasitic infections: Implications for vaccines and diagnostics. Arch. Biochem. Biophys., 2004, 426(2), 182-200.
[] [PMID: 15158669]
Kamena, F.; Liu, X.; Seeberger, P.H. Carbohydrate-Based Vaccines and Immunotherapies; Guo, Z.; Boons, G-J., Eds.; John Wiley & Sons,, 2009, pp. 195-214.
Nikolaev, A.V.; Sizova, O.V. Synthetic neoglycoconjugates of cell-surface phosphoglycans of Leishmania as potential anti-parasite carbohydrate vaccines. Biochemistry (Mosc.), 2011, 76(7), 761-773.
[] [PMID: 21999537]

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