The current project “P8-Transporter” focus on the generation of novel receptor ligandconjugates suitable for targeted receptor-mediated signal transduction and cellular uptake of entities of desired activity and function. Along this line, we designed and synthesise of a novel class of PAR2 (protease activated receptor 2) agonist ligand denoted P8, which is able to specifically bind and activate cell surface human PAR2, in a manner similar to the native activation process mediated by serine proteases. Activation of the receptor also initiates the β- arrestin-mediated and clathrin- and dynamin-dependent endocytosis of PAR2 itself. This mechanism has been demonstrated to play a crucial role for PAR2-mediated uptake of melanin loaded melanosomes into human skin cell, the natural process to protect the skin against UV-irradiation. In this regard, our synthetic PAR2 agonist P8 can be employed to trigger endocytosis and enables the target-specific uptake of molecules, proteins and other biofunctional material or particles into cells, when directly linked to them. Hence, this novel molecular transport system paves the way for a new generation of pharmacological, therapeutical and biotechnological applications, such as target drug delivery or directed cell engineering.
The project has started in 2016 and involves interdisciplinary cooperation partners from the fields of biochemistry (CBIB, Bremen), material science (Advanced Ceramics, Uni Bremen) biophysics (nanoBiomaterials, Uni Bremen), microsystems technology (IMSAS, Uni Bremen) and plant biology (CBIB, Uni Bremen).