Varón Silva

Many proteins are attached to the membrane cell surface by glycosylphosphatidylinositol (GPI) anchors. Additional functions and the effect of these anchors in the function of the anchored proteins are poor understood. Nevertheless, many studies have demonstrated that problems in the GPI biosynthesis can lead to several diseases. It is known that GPI-anchored proteins use the glycolipid for localization in microdomains increasing their interaction with other proteins. To study the function of GPIs and to evaluate its effect in the function of anchored proteins, it is necessary to obtain GPIs and GPI-anchored proteins with well-defined structures.

In this project will be develop new methods for the synthesis of homogeneous GPI-anchored protein and these will be apply for the synthesis of GPI-anchored therapeutic molecules. The proteins INF‑a2a, IL-2 and Hyal-2 will be expressed and anchored to synthetic GPI molecules by using ligation strategies. The proteins will be expressed as protein thioesters and then anchored to synthetic GPI anchors containing a cysteine residue using native chemical ligation, or they will be obtained by using a split intein strategy.  The role of the GPI in the folding of the proteins will be studied and the effect in the activity of the anchored protein will be evaluated in vitro. The methods developed here will be used for the synthesis of other GPI-anchored proteins and to understand the function of GPIs.