Long wavelength optical control of glutamate receptor ion channels using a tetra-<i>ortho</i>-substituted azobenzene derivative

Rullo, Anthony; Reiner, Andreas; Reiter, Alwin; Trauner, Dirk; Isacoff, Ehud Y.; Woolley, G. Andrew

doi:10.1039/c4cc06612j

Cited by 92 publications

(97 citation statements)

References 18 publications

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“…35 Using Trauner's approach to synthesizing tethered ligands for glutamate receptors, we made tetra-ortho-chloro MAG (25), which Isacoff's group showed could be used to control Glu receptor activity with red light in living cells. 61 ■ TETRA-ortho-METHOXY SUBSTITUTED AZONIUM…”

Section: ■ Tetra-ortho-methoxy Substitutionmentioning

confidence: 99%

Red-Shifting Azobenzene Photoswitches for in Vivo Use

et al. 2015

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Recently, there has been a great deal of interest in using the photoisomerization of azobenzene compounds to control specific biological targets in vivo. These azo compounds can be used as research tools or, in principle, could act as optically controlled drugs. Such "photopharmaceuticals" offer the prospect of targeted drug action and an unprecedented degree of temporal control. A key feature of azo compounds designed to photoswitch in vivo is the wavelength of light required to cause the photoisomerization. To pass through tissue such as the human hand, wavelengths in the red, far-red, or ideally near infrared region are required. This Account describes our attempts to produce such azo compounds. Introducing electron-donating or push/pull substituents at the para positions delocalizes the azobenzene chromophore and leads to long wavelength absorption but usually also lowers the thermal barrier to interconversion of the isomers. Fast thermal relaxation means it is difficult to produce a large steady state fraction of the cis isomer. Thus, specifically activating or inhibiting a biological process with the cis isomer would require an impractically bright light source. We have found that introducing substituents at all four ortho positions leads to azo compounds with a number of unusual properties that are useful for in vivo photoswitching. When the para substituents are amide groups, these tetra-ortho substituted azo compounds show unusually slow thermal relaxation rates and enhanced separation of n-π* transitions of cis and trans isomers compared to analogues without ortho substituents. When para positions are substituted with amino groups, ortho methoxy groups greatly stabilize the azonium form of the compounds, in which the azo group is protonated. Azonium ions absorb strongly in the red region of the spectrum and can reach into the near-IR. These azonium ions can exhibit robust cis-trans isomerization in aqueous solutions at neutral pH. By varying the nature of ortho substituents, together with the number and nature of meta and para substituents, long wavelength switching, stability to photobleaching, stability to hydrolysis, and stability to reduction by thiols can all be crafted into a photoswitch. Some of these newly developed photoswitches can be used in whole blood and show promise for effective use in vivo. It is hoped they can be combined with appropriate bioactive targets to realize the potential of photopharmacology.

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Section: ■ Tetra-ortho-methoxy Substitutionmentioning

confidence: 99%

Red-Shifting Azobenzene Photoswitches for in Vivo Use

et al. 2015

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“…Woolley et al describe a method to prepare a photoswitchable azobenzene that can be triggered using red light [89]. The photoresponsive derivative contains an ortho-tetrasubstituted azobenzene attached to a maleimide (Figure 9.14), which can later be covalently attached to the receptor protein via cysteine mutation introduced in the vicinity of the binding site of an ionotropic glutamate receptor.…”

Section: Photocontrol Of Receptors Using Red Lightmentioning

confidence: 99%

“…The photochromic species was covalently attached to phosphate groups on the oligonucleotide strand via two linkage sites, one on the methyl groups on the indoline core and the other on the nitrogen .14 (a) Tetra-ortho-substituted azobenzene-derived glutamate tether for linkage to an ionotropic glutamate receptor, irradiation of the trans-isomer with 630 nm light produces the cis-isomer, and the reverse process is achieved with 450 nm light. (b) The tethered glutamate-azobenzene derivative allows for photocontrol of glutamate binding and channel activation by isomerization of azobenzene from the trans-to the cis-isomer [89]. The planar charged merocyanine allows for more efficient intercalation into the base pairs than the bulkier spiropyran form [99].…”

Section: Spiropyran-modified Oligonucleotide Backbonesmentioning

confidence: 99%

Photochromic Materials in Biochemistry

Wilson

Branda

2016

Photochromic Materials: Preparation, Properties and Applications

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“…Other MAG versions, namely MAG 2P and MAGA 2P , were specifically developed for 2-photon photoswitching [35]. Recently, we described t o Cl-MAG , a tetra- ortho -chloro-substituted azobenzene that can be used for receptor activation with 630 nm light [36]. A significant advantage of the PTL approach is that it relies on a genetically modified receptor, which provides highly specific control over individual receptor subunits, as well as genetic targeting to specific cells.…”

Section: Photoswitchable Tethered Ligandsmentioning

confidence: 99%

Controlling ionotropic and metabotropic glutamate receptors with light: principles and potential

Reiner

Levitz

Isacoff

2015

Current Opinion in Pharmacology

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Light offers unique advantages for studying and manipulating biomolecules and the cellular processes that they control. Optical control of ionotropic and metabotropic glutamate receptors has garnered significant interest, since these receptors are central to signaling at neuronal synapses and only optical approaches provide the spatial and temporal resolution required to directly probe receptor function in cells and tissue. Following the classical method of glutamate photo-uncaging, recently developed methods have added other forms of remote control, including those with high molecular specificity and genetic targeting. These tools open the door to the direct optical control of synaptic transmission and plasticity, as well as the probing of native receptor function in intact neural circuits.

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Long wavelength optical control of glutamate receptor ion channels using a tetra-ortho-substituted azobenzene derivative

Cited by 92 publications

References 18 publications

Red-Shifting Azobenzene Photoswitches for in Vivo Use

Red-Shifting Azobenzene Photoswitches for in Vivo Use

Photochromic Materials in Biochemistry

Controlling ionotropic and metabotropic glutamate receptors with light: principles and potential

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