Description
The project will contribute to the development of novel treatment strategies for chronic inflammatory diseases. The objective of this proposal is to develop compounds that can form the basis for new therapeutics for chronic inflammatory diseases. The project will contribute to the methodology for the development of novel drugs targeting protein-protein interfaces. We will model the interactions of proteins connected with chronic obstructive pulmonary disease and find and test compounds that block these interactions. In the development of novel compounds inhibiting the interaction between PR3 and PLSCR1 we will use both the state-of-the-art computational and experimental molecular biology techniques. The target group are scientists interested in protein-protein and protein-membrane interactions. Collaboration will strengthen the scientific networks between Poland and Norway. The donor partner will contribute to the refinement of the structure of the studied PR3/PLSCR1 complex and the design of inhibitors targeting this protein-protein interface. This partnership will enhance research cooperation in the field of modern pharmacology.
Summary of project results
The outcome of the project was the design and testing of D-peptides as inhibitors of the interactions of proteinase 3 with the membrane. Blocking this interaction would be beneficial in the cure of chronic obstructive pulmonary diseases (COPD). We designed the D-peptides and verified that they do not inhibit the catalytic activity of proteinase 3 but some precluded the binding of proteinase 3 to membranes. Thus the membrane binding pocket of proteinase 3 can be used to further improve the compounds that would block this interaction. We also defined other putative binding sites of proteinase 3 other than the catalytic site. We also delivered software to study how the proteins diffuse near biological membranes.
Summary of bilateral results
The UW group learned at UiB how to perform the surface plasmon resonance (SPR) experiments on the Biacore equipment and for the studied proteinase 3 enzyme. UW and UiB exchanged knowledge on the design of peptides. UiB modeling partner learned which amino acids to use in the design to enable in-house synthesis of these peptides by UW. New grants were not submitted as a result of this collaboration but we plan to consider this in the future if appropriate calls appear.