A Photocaged Microtubule‐Stabilising Epothilone Allows Spatiotemporal Control of Cytoskeletal Dynamics DOI Creative Commons
Carina Schmitt,

Philipp Mauker,

Nynke A. Vepřek

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(43)

Published: July 4, 2024

Abstract The cytoskeleton is essential for spatial and temporal organisation of a wide range cellular tissue‐level processes, such as proliferation, signalling, cargo transport, migration, morphogenesis, neuronal development. Cytoskeleton research aims to study these processes by imaging, or locally manipulating, the dynamics cytoskeletal proteins with high spatiotemporal resolution: which matches capabilities optical methods. To date, no photoresponsive microtubule‐stabilising tool has united all features needed practical high‐precision reagent: low potency biochemically stable non‐illuminated state; then an efficient, rapid, clean photoresponse that generates illuminated plus good solubility at suitable working concentrations; efficient synthetic access. We now present CouEpo , photocaged epothilone reagent combines needs. Its increases approximately 100‐fold upon irradiation violet/blue light reach low‐nanomolar values, allowing photocontrol microtubule in live cells, even generation asymmetries architecture cell dynamics. thus high‐performance compound can support into many microtubule‐associated from biophysics motility, physiology.

Language: Английский

A photo-SAR study of photoswitchable azobenzene tubulin-inhibiting antimitotics identifying a general method for near-quantitative photocontrol DOI Creative Commons
Martin Reynders,

Małgorzata Garścia,

Adrian Müller‐Deku

et al.

Published: May 8, 2024

Here, we performed photo-SAR studies in a series of photoswitchable tubulin inhibiting antimitotics, and discovered that fluorescent antenna motifs permit their single-photon photoisomerisation biological conditions at up to >600 nm; were also able visualise the temporal onset long-term photopharmacological effects, using large-field-of-view microscopy. Previously, azobenzene analogues polymerisation inhibitor combretastatin A4 (PSTs) had been developed optically control microtubule dynamics living systems, with subsecond response time single-cell spatial precision, by reversible situ photoswitching bioactivity near-UV/visible light. First-generation PSTs sufficiently potent for use live cells embryos. However, link between seconds-scale hours-scale remained untested. now used tandem photoswitching/microscopy reveal timing bulk cytostatic effects. Since scope modifications tune photo-structure-activity-relationship or expand PST function unknown, then synthesised panel novel exploring structural variations photoresponse wavelengths lipophilicity, identifying promising blue-shifted are better-compatible GFP/YFP imaging. Taken together, these results can guide new design applications inhibitors. Finally, identified tolerated sites linkers attach functional cargos, tested them "antennas" as reporters. Serendipitously, found antennas greatly enhance long-wavelength photoisomerisation, hitherto un-explored mechanism. This final result will drive progress towards near-quantitative photopharmaceuticals minimal molecular redesign general application scope.

Language: Английский

Citations

1
A photo-SAR study of photoswitchable azobenzene tubulin-inhibiting antimitotics identifying a general method for near-quantitative photocontrol DOI Creative Commons
Martin Reynders,

Małgorzata Garścia,

Adrian Müller‐Deku

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(31), P. 12301 - 12309

Published: Jan. 1, 2024

We develop reagents to optically control microtubule dynamics, with (1) lensless microscopy track their bioactivity; (2) photo-SAR find GFP-compatible reagents; & (3) fluorophore antennas drive single-photon isomerisation even ≥600 nm.

Language: Английский

Citations

1
A Photocaged Microtubule‐Stabilising Epothilone Allows Spatiotemporal Control of Cytoskeletal Dynamics DOI Creative Commons
Carina Schmitt,

Philipp Mauker,

Nynke A. Vepřek

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: July 4, 2024

Abstract The cytoskeleton is essential for spatial and temporal organisation of a wide range cellular tissue‐level processes, such as proliferation, signalling, cargo transport, migration, morphogenesis, neuronal development. Cytoskeleton research aims to study these processes by imaging, or locally manipulating, the dynamics cytoskeletal proteins with high spatiotemporal resolution: which matches capabilities optical methods. To date, no photoresponsive microtubule‐stabilising tool has united all features needed practical high‐precision reagent: low potency biochemically stable non‐illuminated state; then an efficient, rapid, clean photoresponse that generates illuminated plus good solubility at suitable working concentrations; efficient synthetic access. We now present CouEpo , photocaged epothilone reagent combines needs. Its increases approximately 100‐fold upon irradiation violet/blue light reach low‐nanomolar values, allowing photocontrol microtubule in live cells, even generation asymmetries architecture cell dynamics. thus high‐performance compound can support into many microtubule‐associated from biophysics motility, physiology.

Language: Английский

Citations

1
A Photocaged Microtubule‐Stabilising Epothilone Allows Spatiotemporal Control of Cytoskeletal Dynamics DOI Creative Commons
Carina Schmitt,

Philipp Mauker,

Nynke A. Vepřek

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(43)

Published: July 4, 2024

Abstract The cytoskeleton is essential for spatial and temporal organisation of a wide range cellular tissue‐level processes, such as proliferation, signalling, cargo transport, migration, morphogenesis, neuronal development. Cytoskeleton research aims to study these processes by imaging, or locally manipulating, the dynamics cytoskeletal proteins with high spatiotemporal resolution: which matches capabilities optical methods. To date, no photoresponsive microtubule‐stabilising tool has united all features needed practical high‐precision reagent: low potency biochemically stable non‐illuminated state; then an efficient, rapid, clean photoresponse that generates illuminated plus good solubility at suitable working concentrations; efficient synthetic access. We now present CouEpo , photocaged epothilone reagent combines needs. Its increases approximately 100‐fold upon irradiation violet/blue light reach low‐nanomolar values, allowing photocontrol microtubule in live cells, even generation asymmetries architecture cell dynamics. thus high‐performance compound can support into many microtubule‐associated from biophysics motility, physiology.

Language: Английский

Citations

0