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Optical Control of Mitosis with a Photoswitchable Eg5 Inhibitor.

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.

SUBMITTER: Impastato AC

PROVIDER: S-EPMC9533678 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Optical Control of Mitosis with a Photoswitchable Eg5 Inhibitor.

Impastato Anna C AC Shemet Andrej A Vepřek Nynke A NA Saper Gadiel G Hess Henry H Rao Lu L Gennerich Arne A Trauner Dirk D

Angewandte Chemie (International ed. in English) 20220114 9

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 ...[more]

PMID: 34958711

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