Drug Discovery from Protein-Protein Interactions by NMR

Description

In the past few years the search for active compounds that have a therapeutic influence on protein-protein interactions has been intensified. The present work focuses on our attempt to combine methods from molecular and structural biology with computational approaches to identify small organic compounds that are potential protein-protein interaction inhibitors. The biological target used is the complex of crucial proteins in fatty acid biosynthesis, Acp (acyl carrier protein) with AcpS (acyl carrier protein synthase), from Staphylococcus aureus. Both proteins show a high homology, not only to other cocci, at sequence and structural level. Therefore, we can expect that compounds which inhibit the bacterial Acp-AcpS interaction should have antibiotic activity. To analyze the Acp-AcpS interaction more thoroughly, both proteins were produced recombinantly. Peptides containing parts of the proteins (Acp or AcpS) were synthesized and interaction studies of these peptides with the whole proteins were performed using biolayer-interferometry and NMR. Interacting residues between the proteins were identified by titrations and TCS NMR (Transferred cross saturation) experiments. One of the final goals of the experiments described above is to use the available structural information for deriving pharmacophore models, which in turn can then be employed for virtual screening. We have derived pharmacophore models starting from the available Acp-AcpS complex of Staphylococcus aureus (PDB: 4DXE), including information about interacting residues from the NMR experiments.

Period	25 Sept 2017
Event title	17. Österreichische Chemietage 2017
Event type	Conference
Location	AustriaShow on map