Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 57, Issue 37, Pages 11993-11997Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201806976
Keywords
chemo-optogenetics; intracellular transport; multidirectional activity; photoactivated; signaling
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Funding
- Deutsche Forschungsgemeinschaft, DFG [SPP 1623]
- Behrens Weise Stiftung
- European Research Council, ERC (ChemBioAP)
- Knut and Alice Wallenberg Foundation
- DFG Heisenberg Stipend
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The spatiotemporal dynamics of proteins or organelles plays a vital role in controlling diverse cellular processes. However, acute control of activity at distinct locations within a cell is challenging. A versatile multidirectional activity control (MAC) approach is presented, which employs a photoactivatable system that may be dimerized upon chemical inducement. The system comprises second-generation SLF*-TMP (S*T) and photocaged NvocTMP-Cl dimerizers; where, SLF*-TMP features a synthetic ligand of the FKBP(F36V) binding protein, Nvoc is a caging group, and TMP is the antibiotic trimethoprim. Two MAC strategies are demonstrated to spatiotemporally control cellular signaling and intracellular cargo transport. The novel platform enables tunable, reversible, and rapid control of activity at multiple compartments in living cells.
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