Optical Control of Mitosis with a Photoswitchable Eg5 Inhibitor

Impastato, Anna C.; Shemet, Andrej; Vepřek, Nynke A.; Saper, Gadiel; Hess, Henry; Rao, Lu; Gennerich, Arne und Trauner, Dirk (2022): Optical Control of Mitosis with a Photoswitchable Eg5 Inhibitor. In: Angewandte Chemie International Edition, Bd. 61, Nr. 9, e202115846

Abstract

Eg5 is a kinesin motor protein that is responsible for bipolar spindle formation and plays a crucial role during mitosis. Loss of Eg5 function leads to the formation of monopolar spindles, followed by mitotic arrest, and subsequent cell death. Several cell-permeable small molecules have been reported to inhibit Eg5 and some have been evaluated as anticancer agents. We now describe the design, synthesis, and biological evaluation of photoswitchable variants with five different pharmacophores. Our lead compound Azo-EMD is a cell permeable azobenzene that inhibits Eg5 more potently in its light-induced cis form. This activity decreased the velocity of Eg5 in single-molecule assays, promoted formation of monopolar spindles, and led to mitotic arrest in a light dependent way.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department Chemie
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 1433-7851
• Sprache: Englisch