Light-driven release of cucurbit[8]uril from a bivalent cage

Pim J. de Vink; Tim van der Hek; Lucas Brunsveld

doi:10.1039/D1SC01410B

Light-driven release of cucurbit[8]uril from a bivalent cage

Pim J. de Vink, Tim van der Hek, Lucas Brunsveld (Corresponding author)

Research output: Contribution to journal › Article › Academic › peer-review

6 Citations (Scopus)

Abstract

Temporal control over supramolecular systems has great potential for the modulation of binding and assembly events, such as providing orthogonal control over protein activity. Especially light controlled triggering provides unique entries for supramolecular systems to interface in a controlled manner with enzymes. Here we report on the light-induced release of cucurbit[8]uril (CB[8]) from a bivalent cage molecule and its subsequent activation of a proteolytic enzyme, caspase-9, that itself is unresponsive to light. Central to the design is the bivalent binding of the cage with high affinity to CB[8], 100-fold stronger than the UV-inactivated products. The affinity switching occurs in the (sub-)micromolar concentration regime, matching the concentration characteristics required for dimerizing and activating caspase-9 by CB[8]. The light-responsive caged CB[8] concept presented offers a novel platform for tuning and application of switchable cucurbiturils and beyond.

Original language	English
Pages (from-to)	6726-6731
Number of pages	6
Journal	Chemical Science
Volume	12
Issue number	19
DOIs	https://doi.org/10.1039/D1SC01410B
Publication status	Published - 21 May 2021

Funding

This research was funded by the Netherlands Organization for Scientic Research (NWO) through Gravity program 024.001.035 and VICI grant 016.150.366. We thank Bas Rosier for the discussions about caspases.

Funders	Funder number
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	016.150.366, 024.001.035

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Cite this

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abstract = "Temporal control over supramolecular systems has great potential for the modulation of binding and assembly events, such as providing orthogonal control over protein activity. Especially light controlled triggering provides unique entries for supramolecular systems to interface in a controlled manner with enzymes. Here we report on the light-induced release of cucurbit[8]uril (CB[8]) from a bivalent cage molecule and its subsequent activation of a proteolytic enzyme, caspase-9, that itself is unresponsive to light. Central to the design is the bivalent binding of the cage with high affinity to CB[8], 100-fold stronger than the UV-inactivated products. The affinity switching occurs in the (sub-)micromolar concentration regime, matching the concentration characteristics required for dimerizing and activating caspase-9 by CB[8]. The light-responsive caged CB[8] concept presented offers a novel platform for tuning and application of switchable cucurbiturils and beyond.",

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Light-driven release of cucurbit[8]uril from a bivalent cage

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