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Probing Trypanosoma brucei Glycosylphosphatidylinositol Biosynthesis Using Novel Precursor‐Analogues
Author(s) -
Urbaniak Michael D.,
Crossman Arthur,
Ferguson Michael A. J.
Publication year - 2008
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2008.00688.x
Subject(s) - diacylglycerol kinase , trypanosoma brucei , biosynthesis , biochemistry , chemistry , inositol , biology , enzyme , protein kinase c , receptor , gene
Glycosylphosphatidylinositol precursor‐analogues were synthesized in which the natural diacylglycerol lipid was replaced with either of two steroidal moieties. The ability of the steroidal glycosylphosphatidylinositol precursor‐analogues to prime the glycosylphosphatidylinositol biosynthetic pathway was assessed in a trypanosomal cell‐free system. The N‐ acetyl‐ d ‐glucosaminylphosphatidylinositol de‐ N ‐acetylase was only able to act upon the N ‐acetylglucosamine form of one of the two analogues. However, the glucosamine form of both analogues could be mannosylated, but neither were inositol‐acylated nor modified with ethanolamine phosphate. The use of alternative groups, such as sterols, in place of the natural diacylglycerol lipid may enable the production of more drug‐like, substrate‐based inhibitors.