The functioning of living organisms is to a large extent dependent on the interplay between the biomolecules they are composed of. Protein-protein interactions (PPIs) are a basic mechanism that regulates this interplay. Consequently, in the past few years the search for active compounds that have a therapeutic influence on protein-protein interactions has been intensified. In most cases these compounds are inhibitors of these interactions.
The aim of the project was to use a bacterial enzyme system in order to develop a prototypical workflow for the generation of hit structures for inhibition of protein-protein interactions (PPIs). Starting from the ACP/ACPS-system of Staphylococcus aureus peptides were identified that inhibit the ACP-ACPS-interaction. Peptide-ACP-interactions as well as ACPS-ACP-interactions were analyzed by NMR experiments. The insights obtained, together with structural information from available X-ray structures, led to the development of pharmacophore models that were used in virtual screening to identify potential small molecules PPI inhibitors.
The project was funded by the Austrian Research Promotion Agency under the 15th call for the BRIDGE 1 programme line.