Paper Presentation 8th November 2013 Rijeesh K

A red-shifted, fast-relaxing azobenzene photoswitch for visible light control of an ionotropic glutamate receptor Michael A. Kienzler‡, Andreas Reiner‡, Eric Trautman, Stan Yoo, Dirk Trauner*, Ehud Y. Isacoff* Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, and Department of Chemistry and Center for Integrated Protein Science, Ludwig-Maximilians-Universitat, Munich, Butenandtstr

Transmembrane Receptor………… Trans membrane receptors allow a cell to communicate with its environment in response to a variety of input signals. These can be changes in the concentration of ligands (e.g. hormones or neurotransmitters),temperature, pressure (e.g. acoustic waves or touch), Trans membrane potential, or light intensity.

Glutamate Receptor………… Ionotropic glutamate receptors (iGluRs) play a central role in synaptic transmission. These ligand-gated ion channels respond to the neurotransmitter glutamate released from vesicles on the presynaptic side. Upon glutamate binding, iGluRs generate a depolarizing current, which results in an excitatory postsynaptic potential. Alzheimers disease, epilepsy, and neuronal damage from stroke, and have therefore been very important neuro pharmacological targets

Three strategies used in optochemical genetic..

The patch-clamp technique..

Previous studies…………

Previous studies…………

In this study……

Comparison between …… In this study Previous studies Trans → cis at 380nm Trans → cis at 462nm Thermal back 25.5 min Thermal back 0.71 s i.e. 2,200 time faster cis→ trans at 500nm Single wavelength dependant This modified azobenzene core is activated at one wavelength in the visible part of the spectrum and the rapidly relaxes back to inactive trans state in the dark makes it more important in neuroscience application.

Synthesis LMAG0 ……

Result and Discussion……

Result and Discussion……

Conclusion. Synthesis first PTL with a red-shifted azobenzene core. LMAG0 operates a potent photoswitch for LIGluR made from excitatory kainate receptor GluK2. Fast and spontaneous deactivation is an important functional feature that could be generally applicable to PTLs with low affinity ligands. The red-shift and single wavelength should enable deeper penetration in brain tissue while minimizing photo-toxicity and achieving control with only one light source.

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