Cell‐Permeant and Photocleavable Chemical Inducer of Dimerization |
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| Authors: | Mirjam Zimmermann Ruben Cal Elia Janett Viktor Hoffmann Prof. Dr. Christian G. Bochet Prof. Dr. Edwin Constable Dr. Florent Beaufils Prof. Dr. Matthias P. Wymann |
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| Affiliation: | 1. University of Basel, Department of Biomedicine, Mattenstrasse 28, Basel (Switzerland);2. University of Fribourg, Department of Chemistry, Chemin du Musée 9, Fribourg (Switzerland);3. University of Basel, Department of Chemistry, Spitalstrasse 51, Basel (Switzerland) |
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| Abstract: | Chemical inducers of dimerization (CIDs) have been developed to orchestrate protein dimerization and translocation. Here we present a novel photocleavable HaloTag‐ and SNAP‐tag‐reactive CID (MeNV‐HaXS) with excellent selectivity and intracellular reactivity. Excitation at 360 nm cleaves the methyl‐6‐nitroveratryl core of MeNV‐HaXS. MeNV‐HaXS covalently links HaloTag‐ and SNAP‐tag fusion proteins, and enables targeting of selected membranes and intracellular organelles. MeNV‐HaXS‐mediated translocation has been validated for plasma membrane, late endosomes, lysosomes, Golgi, mitochondria, and the actin cytoskeleton. Photocleavage of MeNV‐HaXS liberates target proteins and provides access to optical manipulation of protein relocation with high spatiotemporal and subcellular precision. MeNV‐HaXS supports kinetic studies of protein dynamics and the manipulation of subcellular enzyme activities, which is exemplified for Golgi‐targeted cargo and the assessment of nuclear import kinetics. |
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| Keywords: | chemical inducers of dimerization fusion proteins photocleavable linkers photolysis protein– protein interactions |
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