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Photoswitchable epothilone-based microtubule stabilisers allow GFP-imaging-compatible, optical control over the microtubule cytoskeleton

info:eu-repo/semantics/OpenAccess ;ISSN: 1433-7851 ;EISSN: 1521-3773

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  • Title:
    Photoswitchable epothilone-based microtubule stabilisers allow GFP-imaging-compatible, optical control over the microtubule cytoskeleton
  • Author: Gao, Li ; Meiring, Joyce C M ; Heise, Constanze ; Rai, Ankit ; Müller-Deku, Adrian ; Akhmanova, Anna ; Thorn-Seshold, Julia ; Thorn-Seshold, Oliver
  • Subjects: Bioorganic Chemistry ; Catalysis ; General Chemistry ; Microtubule Inhibitor ; Natural Products ; Photopharmacology ; Photoswitch
  • Description: Optical methods to modulate microtubule dynamics show promise for reaching the micron- and millisecond-scale resolution needed to decrypt the roles of the cytoskeleton in biology. However, optical microtubule stabilisers are under-developed. We introduce “STEpos” as GFP-orthogonal, light-responsive epothilone-based microtubule stabilisers. They use a novel styrylthiazole photoswitch in a design to modulate hydrogen-bonding and steric effects that control epothilone potency. STEpos photocontrol microtubule dynamics and cell division with micron- and second-scale spatiotemporal precision. They substantially improve potency, solubility, and ease-of-use compared to previous optical microtubule stabilisers, and the structure-photoswitching-activity relationship insights in this work will guide future optimisations. The STEpo reagents can contribute greatly to high-precision research in cytoskeleton biophysics, cargo transport, cell motility, cell division, development, and neuroscience.
  • Creation Date: 2022-03
  • Language: English
  • Identifier: ISSN: 1433-7851
    EISSN: 1521-3773
  • Source: Utrecht University Repository
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