A Red-Shifted,
Fast-Relaxing Azobenzene Photoswitch
for Visible Light Control of an Ionotropic Glutamate Receptor
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Abstract
The
use of azobenzene photoswitches has become a dependable method
for rapid and exact modulation of biological processes and material
science systems. The requirement of ultraviolet light for azobenzene
isomerization is not ideal for biological systems due to poor tissue
penetration and potentially damaging effects. While modified azobenzene
cores with a red-shifted <i>cis</i>-to-<i>trans</i> isomerization have been previously described, they have not yet
been incorporated into a powerful method to control protein function:
the photoswitchable tethered ligand (PTL) approach. We report the
synthesis and characterization of a red-shifted PTL, L-MAG0<sub>460</sub>, for the light-gated ionotropic glutamate receptor LiGluR. In cultured
mammalian cells, the LiGluR+L-MAG0<sub>460</sub> system is activated
rapidly by illumination with 400–520 nm light to generate a
large ionic current. The current rapidly turns off in the dark as
the PTL relaxes thermally back to the <i>trans</i> configuration.
The visible light excitation and single-wavelength behavior considerably
simplify use and should improve utilization in tissue