A synthetic acceptor substrate for Trypanosoma brucei UDP-Gal : GPI anchor side-chain α-galactosyltransferases

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 15, 1998, Pages 2051-2054

  Brown, Jillian R ^a,b   Smith, Terry K ^b   Ferguson, Michael A J ^b   Field, Robert A ^a  

^a UNIVERSITY OF ST ANDREWS   (United Kingdom)

^b UNIVERSITY OF DUNDEE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CARBOHYDRATE DERIVATIVE; GALACTOSE ALPHA 1,3 (MANNOSE ALPHA 1,6)MANNOSE ALPHA O OCTYL; GALACTOSYLTRANSFERASE; UNCLASSIFIED DRUG; URIDINE DIPHOSPHATE GALACTOSE; VARIANT SURFACE GLYCOPROTEIN;

ANTIPROTOZOAL ACTIVITY; ARTICLE; CARBOHYDRATE SYNTHESIS; DRUG SYNTHESIS; ENZYME SUBSTRATE; ENZYME SUBSTRATE COMPLEX; GOLGI COMPLEX; MEMBRANE BINDING; PARASITE VIRULENCE; PROTEIN GLYCOSYLATION; STRUCTURE ACTIVITY RELATION; TRYPANOSOMA BRUCEI;

ANIMALS; BIOTRANSFORMATION; CARBOHYDRATE SEQUENCE; GALACTOSYLTRANSFERASES; GLYCOSYLPHOSPHATIDYLINOSITOLS; MOLECULAR SEQUENCE DATA; SUBSTRATE SPECIFICITY; TRYPANOSOMA BRUCEI BRUCEI; URIDINE DIPHOSPHATE GALACTOSE; VARIANT SURFACE GLYCOPROTEINS, TRYPANOSOMA;

EID: 0032483111     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00359-X     Document Type: Article

References (20)

1. 1. McConville, M.J.; Ferguson, M.A.J. Biochem. J., 1993, 294, 305-324.
2. 2. Ferguson, M.A.J.; Homans, S.W.; Dwek, R.A.; Rademacher, T.W. Science, 1988, 239, 753-759.
3. 3. Mehlen, A.; Richardson, J.M.; Ferguson, M.A.J. J. Mol. Biol., 1998, 277, 379-392.
4. 4. Cross, G.A.M. Annu. Rev. Immunol., 1990, 8, 83-110.
5. 5. Ferguson, M.A.J. Parasitology Today, 1994, 10, 48-52. Overath, P.; Chandhri, M.; Steverding, D.; Zieglbauer, K. Parasitology Today, 1994, 10, 53-58.
6. 5. Ferguson, M.A.J. Parasitology Today, 1994, 10, 48-52. Overath, P.; Chandhri, M.; Steverding, D.; Zieglbauer, K. Parasitology Today, 1994, 10, 53-58.
7. 6. Pingel, S.; Field, R.A.; Duszenko, M.; Güther, M.L.S.; Ferguson, M.A.J. Biochem J., 1995, 309, 877-882.
8. 7. Ziegler, T.; Dettmann, R.; Duszenko, M.; Kolb, V. Carbohydr. Res., 1996, 295, 7-23.
9. 8. For recent studies that employ synthetic substrates to investigate other aspects of GPI biosynthesis see: Sharma, D.K.; Smith, T.K.; Crossman, A.; Brimacombe, J.S.; Ferguson, M.A.J. Biochem. J., 1997, 328, 171-177 and references cited therein. Smith, T.K.; Sharma, D.K.; Crossman, A.; Dix, A.; Brimacombe, J.S.; Ferguson, M.A.J. EMBO J., 1997, 16, 6667-6675. Doerrler, W.T.; Ye, J.; Falck, J.R.; Lehrman, M.A. J. Biol. Chem., 1996, 271, 27031-27038. Ye, J.H; Doerrler, W.T.; Lehrman, M.A.; Falck, J.R. Bioorg. Med. Chem. Lett., 1996, 6, 1715-1718
10. 8. For recent studies that employ synthetic substrates to investigate other aspects of GPI biosynthesis see: Sharma, D.K.; Smith, T.K.; Crossman, A.; Brimacombe, J.S.; Ferguson, M.A.J. Biochem. J., 1997, 328, 171-177 and references cited therein. Smith, T.K.; Sharma, D.K.; Crossman, A.; Dix, A.; Brimacombe, J.S.; Ferguson, M.A.J. EMBO J., 1997, 16, 6667-6675. Doerrler, W.T.; Ye, J.; Falck, J.R.; Lehrman, M.A. J. Biol. Chem., 1996, 271, 27031-27038. Ye, J.H; Doerrler, W.T.; Lehrman, M.A.; Falck, J.R. Bioorg. Med. Chem. Lett., 1996, 6, 1715-1718
11. 8. For recent studies that employ synthetic substrates to investigate other aspects of GPI biosynthesis see: Sharma, D.K.; Smith, T.K.; Crossman, A.; Brimacombe, J.S.; Ferguson, M.A.J. Biochem. J., 1997, 328, 171-177 and references cited therein. Smith, T.K.; Sharma, D.K.; Crossman, A.; Dix, A.; Brimacombe, J.S.; Ferguson, M.A.J. EMBO J., 1997, 16, 6667-6675. Doerrler, W.T.; Ye, J.; Falck, J.R.; Lehrman, M.A. J. Biol. Chem., 1996, 271, 27031-27038. Ye, J.H; Doerrler, W.T.; Lehrman, M.A.; Falck, J.R. Bioorg. Med. Chem. Lett., 1996, 6, 1715-1718
12. 8. For recent studies that employ synthetic substrates to investigate other aspects of GPI biosynthesis see: Sharma, D.K.; Smith, T.K.; Crossman, A.; Brimacombe, J.S.; Ferguson, M.A.J. Biochem. J., 1997, 328, 171-177 and references cited therein. Smith, T.K.; Sharma, D.K.; Crossman, A.; Dix, A.; Brimacombe, J.S.; Ferguson, M.A.J. EMBO J., 1997, 16, 6667-6675. Doerrler, W.T.; Ye, J.; Falck, J.R.; Lehrman, M.A. J. Biol. Chem., 1996, 271, 27031-27038. Ye, J.H; Doerrler, W.T.; Lehrman, M.A.; Falck, J.R. Bioorg. Med. Chem. Lett., 1996, 6, 1715-1718
13. 9. Garegg, P.J.; Oscarson, S.; Tiden, A-K. Carbohydr. Res., 1990, 203, c3-c8.
14. 10. Oscarson, S.; Tiden, A-K. Carbohydr. Res., 1993, 247, 323-328.
15. 11. Kartha, K.P.R.; Field, R.A. Tetrahedron Lett., 1997, 38, 8233-8237
16. 9 proved extremely slow. Whilst the more forcing coupling conditions reported here give an anomeric mixture of trisaccharides, sufficient material was obtained to proceed with biochemical studies.
17. 16]: m/z 616.7. Found [M-1]-: m/z 615.0
18. 14. Further experimental details can be found in : Brown, J. Ph.D. Thesis, 1997, University of Dundee, Dundee, UK. See also reference 6 for similar experimental protocols.
19. 15. Endogenous diacylglycerol-containing glycolipids were removed by treatment with base prior to analysis.
20. 16. It is important to note that the products formed from (1) are only present in radiochemical quantities in the assay, and hence at very low concentration. It is conceivable that at higher concentrations the α-Gal-(1) adduct would undergo further galactosylation, as expected of a GPI pathway substrate.