Actin- and Microtubule-Targeting Bioprobes: Their Binding Sites and Inhibitory Mechanisms

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  • USUI Takeo
    Graduate School of Life and Environmental Sciences, University of Tsukuba

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Actin filaments and microtubules play important biological functions in mammalian cells, such as mitosis, cytokinesis, cell signaling, intracellular transport, and cell motility. Therefore, small molecules that interact with these cytoskeletons are expected to be useful not only as antitumor agents, but also as tools for understanding a wide variety of the cellular functions of cytoskeletons. A large number of compounds have been reported as anti-microtubule or anti-actin agents, but only a few compounds have been clarified as to their binding sites on target molecules and their inhibition mechanisms. Here, I describe our recent research into anti-actin and anti-microtubule natural products. Some inhibitors contain active moieties, such as α,β-unsaturated δ-lactone or allely epoxide, in their structure, and covalently bind to their target molecules. Furthermore, some compounds show new inhibition mechanisms by binding on novel sites in target molecules.

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