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Cell‐Permeant and Photocleavable Chemical Inducer of Dimerization
Author(s) -
Zimmermann Mirjam,
Cal Ruben,
Janett Elia,
Hoffmann Viktor,
Bochet Christian G.,
Constable Edwin,
Beaufils Florent,
Wymann Matthias P.
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201310969
Subject(s) - chemistry , endosome , intracellular , golgi apparatus , microbiology and biotechnology , biophysics , organelle , brefeldin a , biochemistry , cell , biology
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.