Probing Trypanosoma brucei glycosylphosphatidylinositol biosynthesis using novel precursor-analogues

Urbaniak, Michael D. and Crossman, Arthur and Ferguson, Michael A. J. (2008) Probing Trypanosoma brucei glycosylphosphatidylinositol biosynthesis using novel precursor-analogues. Chemical Biology and Drug Design, 72 (2). pp. 127-132. ISSN 1747-0277

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Abstract

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.

Item Type:
Journal Article
Journal or Publication Title:
Chemical Biology and Drug Design
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1300/1303
Subjects:
?? animalscell-free systemglycosylphosphatidylinositolsmolecular structuresteroidssubstrate specificitytrypanosoma brucei bruceibiochemistrymolecular medicine ??
ID Code:
66393
Deposited By:
Deposited On:
17 Sep 2013 08:08
Refereed?:
Yes
Published?:
Published
Last Modified:
15 Jul 2024 14:12