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Probing the role of sulfation (Probing sulfation)
Date du début: 1 mars 2014, Date de fin: 28 févr. 2018 PROJET  TERMINÉ 

The aim of the research proposed here is to investigate the role of sulfation in general, and more specifically in the context of chemokine signaling. For this purpose, tools will be developed that can be used to study and to interfere with sulfation. First of all, activity-based probes (ABPs) will be synthesized for both sulfotransferases and sulfatases by modifying known inhibitors with a (photo)reactive group. The resulting ABPs will be used to establish the activity of the different enzymes in the presence and absence of chemokines.Furthermore, a protein modification strategy will be developed that will allow the preparation of cells containing a well-defined sulfation pattern. The heterogeneous set of sulfated molecules that is presented by cells under normal conditions hampers the study of specific sulfation reactions in chemokine signaling. Affinity of chemokines for their cognate receptor is regulated by sulfation. The ability to introduce a homogeneous sulfation pattern that can be modified at will, should facilitate the study of sulfation’s importance in a systematic fashion. Although these tools will be used initially to investigate the role of sulfation in chemokine signaling, they may also be useful to study other processes that involve sulfation, like host-pathogen interactions, hormone-dependent cancers and lysosomal storage diseases