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Updated: Dec 24, 2025

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
Published on: March 5, 2018
Intracellular Photoactivation of Caspase-3 by Molecular Glues for Spatiotemporal Apoptosis Induction
Nina B Hentzen1, Rina Mogaki2, Saya Otake2
1Laboratorium für Organische Chemie, ETH Zürich, D-CHAB, Vladimir-Prelog-Weg 3, 8093, Zürich, Switzerland.
Abstract:
Caspase-3 (Casp-3) is an enzyme that efficiently induces apoptosis, a form of programmed cell death. We report a dendritic molecular glue PCGlue that enables intracellular delivery of Casp-3 and its photoactivation. PCGlue carrying multiple guanidinium (Gu+) ion pendants via photocleavable linkages can tightly adhere to Casp-3 and deliver it into the cytoplasm mainly by direct penetration through the plasma membrane. Casp-3, whose surface is covered by PCGlue, is unable to interact with its cellular substrates and can therefore not induce apoptosis. However, upon exposure to UV or two-photon near-infrared (NIR) light, PCGlue is cleaved off to liberate Casp-3, triggering the apoptotic signaling cascade. This intracellular photoactivation of Casp-3 allows spatiotemporal induction of apoptosis in irradiated cells.
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