2 research outputs found
An Optimized Glutamate Receptor Photoswitch with Sensitized Azobenzene Isomerization
A new
azobenzene-based photoswitch, <b>2</b>, has been designed
to enable optical control of ionotropic glutamate receptors in neurons
via sensitized two-photon excitation with NIR light. In order to develop
an efficient and versatile synthetic route for this molecule, a modular
strategy is described which relies on the use of a new linear fully
protected glutamate derivative stable in basic media. The resulting
compound undergoes one-photon <i>trans</i>ā<i>cis</i> photoisomerization via two different mechanisms: direct
excitation of its azoaromatic unit and irradiation of the pyrene sensitizer,
a well-known two-photon sensitive chromophore. Moreover, <b>2</b> presents large thermal stability of its <i>cis</i> isomer,
in contrast to other two-photon responsive switches relying on the
intrinsic nonlinear optical properties of pushāpull substituted
azobenzenes. As a result, the molecular system developed herein is
a very promising candidate for evoking large photoinduced biological
responses during the multiphoton operation of neuronal glutamate receptors
with NIR light, which require accumulation of the protein-bound <i>cis</i> state of the switch upon repeated illumination
Two-Photon Neuronal and Astrocytic Stimulation with Azobenzene-Based Photoswitches
Synthetic photochromic compounds
can be designed to control a variety
of proteins and their biochemical functions in living cells, but the
high spatiotemporal precision and tissue penetration of two-photon
stimulation have never been investigated in these molecules. Here
we demonstrate two-photon excitation of azobenzene-based protein switches
and versatile strategies to enhance their photochemical responses.
This enables new applications to control the activation of neurons
and astrocytes with cellular and subcellular resolution