ProtoQSAR develop the project PANACHE: Production of next generation peptidomimetics targeted towards pannexins and connexins as novel therapeutics in the treatment of inflammatory cardiovascular, hepatic and joint diseases.
The project is funded by the European Commission through the program “Horizon 2020 – Research and Innovation Framework Programme” through the convocatory FETOPEN-RIA-2019-01
The modulation of membrane-bound proteins by peptides and peptidomimetics is receiving increasing attention from both academia and industry. Among such proteins are pannexin1 (Panx1), connexin (Cx) 43 and Cx32 that form hemichannels at the plasma membrane surface. These hemichannels mediate cellular communication and have emerged as key players in inflammation. This carries translational relevance, as hemichannel inhibition could represent an innovative strategy for the treatment of a plethora of diseases. However, a hurdle in clinical exploration is the lack of appropriate hemichannel inhibitors. PANACHE therefore is a timely project, as it will generate modified peptides and peptidomimetics targeted against Panx1, Cx43 and Cx32, using unprecedented conformational molding in order to deliver selective lead compounds towards therapeutically promising hemichannel inhibitors. As proof-of-concept, the generated peptide analogues derived from moieties of Panx1, Cx43 and Cx32 will be tested for their potential to alleviate pathological features in animal models of inflammatory diseases in the cardiovascular system, liver and joints. This will be accomplished by joining academic and industrial scientists from the chemical, chemo-informatics and biomedical fields as well as by relying on in vitro and in silico studies, animal experimentation and testing human material. PANACHE will allow taking a leap forward to the realization of its long-term vision, namely the production of metabolically robust and selective peptidomimetics that can be used for the establishment of a generic approach to synergize current therapy of hard-to-treat inflammatory diseases. Hence, PANACHE is a foundational project, laying the basis for follow-up initiatives not only to scrutinize the versatile anti-inflammatory therapeutic actions of the Panx1, Cx43 and Cx32 peptidomimetics as such, but also to develop peptide-based probes raised against similar challenging targets with other applications.