Authors: de Lederkremer, R.M.; Bertello, L.E.

Source: Current Pharmaceutical Design, Volume 7, Number 12, 1 August 2001 , pp. 1165-1179(15)

Publisher: Bentham Science Publishers

Abstract:

The most important glycoproteins of trypanosomatids are anchored by glycoinositolphospholipids (GIPLs) to their plasma membrane. In addition, free GIPLs have been described, for instance the lipopeptidophosphoglycan (LPPG) which is a major component of the surface of T. cruzi epimastigotes. An inositolphosphoceramide (IPC) is part of the LPPG and of glycoproteins present in different stages of T. cruzi. Ceramide was not found in mammal GIPL-anchors. The lipid moieties in T. cruzi anchors can be quite variable. However, no diacylglycerol (DAG) was found in contrast with the African trypanosomes. In GIPLs of epimastigotes collected at the logarithmic phase of growth both, 1-O-hexadecyl- 2-O-palmitoylglycerol and ceramide were identified. Lignoceroylsphinganine is the major ceramide, however, no lignoceric acid was detected when analysing the candidate precursors IPCs, in any of the stages of T. cruzi. An alkylglycerol has been found either as a lyso species in the Tc85 glycoprotein of trypomastigotes or acylated as in the 1G7 anchor of metacyclic forms and in the mucins of epimastigote forms. The lipid in the mucins is replaced by ceramide when the parasite differentiates to metacyclic forms. Also, in the Ssp-4 glycoprotein characteristic of amastigotes, a ceramide was identified as the anchor lipid. These variations suggest that a remodelling mechanism is working in T. cruzi. On the other hand, the oligosaccharide core in the GIPLs of T. cruzi is substituted with galactofuranose. This monosaccharide is found only in the pyranose configuration in mammalian glycoproteins and glycolipids. Thus, the biosynthetic steps for the introduction of galactofuranose and ceramide in the anchors of T. cruzi are good targets for the development of therapeutic agents.

Keywords: Glycoinositolphospholipids; Proteins; Trypanosoma cruzi; glycoproteins; lipopeptidophosphoglycan(LPPG); diacylglycerol (DAG); alkylglycerol; glycoinositolphospholipid(GIPL); Glycosylphosphatidylinositol (GPI); GLYCOINOSITOLPHOSPHOLIPIDS

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1381612013397519

Publication date: 2001-08-01

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  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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