TFF2IBDrug · TFF2 production and molecular mechanism studies to support new therapeutic approaches for gut diseases.

Inflammatory bowel diseases (IBD) are chronic gastrointestinal (GI) conditions, which affect approximately 1.3 and 2 million people in Europe and North America, respectively, with a growing number of incidences in Asia as well. Currently, existing therapies only alleviate the symptoms and suppress the inflammation, but dont promote gut repair. The development of novel therapies is limited by a lack of understanding of the underlying processes of gut healing and repair. Although trefoil family factors (TFF) are major players in gut epithelium restitution and repair, very little is known about their molecular mechanisms and interaction partners. In this project, I will attempt to close this knowledge gap and will focus on trefoil family factor 2 (TFF2). The proposed project aims to identify TFF2 interaction partners (i), study their structure-activity relationships (ii) and produce TFF2-based peptidomimetics (iii). I will use chemical synthesis coupled with structure elucidation to design and produce TFF2 photoactivatable probes for the identification of TFF2 interaction partners. Then structure-activity relationship studies of TFF2 and identified partners will be carried out to define structural determinants of binding and activity. Based on this knowledge I will design novel TFF2-based peptidomimetics and study their stability, binding to TFF2 targets, and effect on epithelial restitution. The proposed project will deliver fundamental insights into molecular mechanisms of gut healing and yield a set of novel peptidomimetics, which could serve as leads for further development of therapies for IBD and GI conditions.