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 |
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Pages (from-to) | 6726-6731 |
Number of pages | 6 |
Journal | Chemical Science |
Volume | 12 |
Issue number | 19 |
DOIs | |
Publication status | Published - 21 May 2021 |
Funding
This research was funded by the Netherlands Organization for Scientic 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 |
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Nederlandse Organisatie voor Wetenschappelijk Onderzoek | |
Nederlandse Organisatie voor Wetenschappelijk Onderzoek | 016.150.366, 024.001.035 |