Design and synthesis of tailored human caseinolytic protease P inhibitors

Gronauer, Thomas F.; Mandl, Melanie M.; Lakemeyer, Markus; Hackl, Mathias W.; Messner, Martina; Korotkov, Vadim S.; Pachmayr, Johanna und Sieber, Stephan A. (2018): Design and synthesis of tailored human caseinolytic protease P inhibitors. In: Chemical Communications, Bd. 54, Nr. 70: S. 9833-9836

Abstract

Human caseinolytic protease P (hClpP) is important for degradation of misfolded proteins in the mitochondrial unfolded protein response. We here introduce tailored hClpP inhibitors that utilize a steric discrimination in their core naphthofuran scaffold to selectively address the human enzyme. This novel inhibitor generation exhibited superior activity compared to previously introduced betalactones, optimized for bacterial ClpP. Further insights into the bioactivity and binding to cellular targets were obtained via chemical proteomics as well as proliferation- and migration studies in cancer cells.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department für Pharmazie - Zentrum für Pharmaforschung
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 1359-7345
• Sprache: Englisch