Glycosylphosphatidylinositols (GPIs)

Glycosylphosphatidylinositols (GPIs)

Many eukaryotic proteins are attached to the cell membrane by a glycosylphosphatidylinositol unit. This glycolipid contains a core pseudo pentasaccharide chain, a lipid part that is usually a phosphatidyldiacyl glycerol and a phosphatidylethanolamine that connects the glycolipid unit to the protein. The GPI core can have additional modifications depending on the cell type, the most common being phosphorylation, glycosylation or acylation (Figure 1).

<em>Figure 1. Structure of a Glycosylphosphatidylinositol (GPI) anchor</em>
Figure 1. Structure of a Glycosylphosphatidylinositol (GPI) anchor

During the last years, the group has been working in the development of a general synthetic strategy to obtain GPIs. By using this strategy, we have successfully obtained GPI molecules from parasites (T. gondii, T. congolense, T. brucei and P. falciparum) and from mammalian cells. Furhermore, we are working in the improvement of this strategy to add complex modifications such as glycan branches, phosphorylations or fluorescence tags as well as in the development of new strategies that allow the synthesis of GPIs having unsaturated lipids.

<em>Figure 2. General scheme for the synthesis of GPI-anchored proteins</em>
Figure 2. General scheme for the synthesis of GPI-anchored proteins

Additional to the synthesis of GPI-anchors, we are investigating the structure of GPIs and the semi-synthesis of GPI-anchored proteins (GPI-APs). To obtain homogeneous GPI-APs, we rely on a combination of molecular biology methods to express the proteins and on ligation strategies to conect them with synthetic GPIs.

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