Periplasmic target-inhibition by natural products and cell wall translocation of inhibitors (A12)

• Subject Area: Pharmacy
• Term: from 2011 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 32152271

Mode of action studies of MraY translocase and bacterial signal peptidase I (SPase) inhibitors will be the focus of this project. We want to understand what structural moieties of uridylpeptides and arylomycins are responsible for target inhibition at the periplasmic surface of the cell membrane. Precursordirected and combinatorial biosynthesis will yield new uridylpeptides for structure-activity-relationship studies. Arylomycins with various non-natural biaryl- and acyl chain structures are obtained from mutasynthesis and semisynthesis for SPase-investigations. With altered arylomycin structures, we will study the affinity of SPase towards this inhibitor class.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 766: The Bacterial Cell Envelope: Structure, Function and Infection Interface
• Applicant Institution: Eberhard Karls Universität Tübingen
• Project Heads: Professorin Dr. Stephanie Grond; Privatdozent Dr. Bertolt Gust