Optopharmacology

View Optopharmacology & Caged Compounds range

What is optopharmacology?

  • Optopharmacological tools offer the ability to control neuronal activity through light-activatable control of molecules
  • These tools enable the manipulation and interrogation of brain function with low invasiveness and high spatiotemporal precision 
  • In comparison to optogenetics which enables the ability to control neuronal excitation/inhibition at a network level, optopharmacology enables control at a molecular level

Optopharmacological Research Tools Available from Hello Bio


Caged Compounds

Caged compounds are becoming widely used in neuroscience as they enable the optical manipulation of neuronal circuits. Photoreleasable neurotransmitters such as glutamate and GABA can be used to activate or inhibit neuronal processes, single neurons, or groups of neurons. Combining this with functional imaging allows for monitoring and controlling of neuronal activity, providing an entirely optical method for analysis of neural circuits.

How does "caging" work?
  • Caged compounds are light-sensitive probes that functionally encapsulate biomolecules in an inactive form.
  • The mechanism behind the caging technique involves a molecule of interest being rendered biologically inert (or "caged") by a chemical modification with a photoremovable protecting group [1].
  • Light-activation results in a concentration jump of the biologically active molecule that can bind to its cellular receptor, switching on/off the targeted process [1]. 

Discover Hello Bio's range of high quality yet affordable caged compounds:

MNI-caged glutamate

Form of glutamate linked to photo-protecting group 4-methoxy-7-nitroindolinyl (MDI). MNI-caged glutamate rapidly and efficiently releases L-glutamate by photolysis (300-380nm excitation).

Uses:

  • Suitable for use with one- and two-photon uncaging microscopy
  • Optically compatible with other chromophores including GFP, YFP and most Ca2+ dyes
  • Can be used for in situ studies of fast synaptic glutamate receptors                                     

MNI-glutamate [295325-62-1] Chemical Structure

MNI-caged γ-DGG (MNI-Caged γ-D-Glutamyl-Glycine)

Novel, caged, fast-equilibrating version of the low-affinity competitive glutamate antagonist γ-DGG. Releases γ-DGG by photolysis (e.g. by flashlamp or laser photolysis). 

Uses:

  • Suitable for use as a synaptic probe
  • Photolysis of MNI-caged γ-DGG resolves timing and extent of transmitter activation of receptors in glutamatergic transmission

                                                            

MNI-DGG Chemical Structure

RuBi glutamate

Caged-glutamate compound based on ruthenium photochemistry. Can be excited with visible wavelengths and after one- or two-photon excitation releases glutamate in less than 50 ns.

Uses

  • Enables the photoactivation of neuronal dendrites and circuits with visible or two-photon light sources, achieving single cell, or even single spine, precision.
  • RuBi-Glutamate has relatively high absorption cross section in the visible (blue) and a high quantum efficiency of uncaging which allows use at low concentrations (e.g. lower concentrations than MNI-Glu).

                                              

 RuBi-Glutamate Chemical Structure

JF-NP-26 (Caged-Raseglurant)

Novel, inactive photocaged derivative of raseglurant / ADX-10059 (the mGlu5 receptor negative allosteric modulator (NAM)).

Uses:

  • Illuminated and uncaged by violet light (405nM), releasing raseglurant with spatial and temporal precision to allow local modulation of mGlu5 receptors
  • Active in vivo, when administered systemically and activated by LED-based illumination induces JF-NP-26-mediated, light-dependent analgesia in both neuropathic and acute/tonic inflammatory pain models.

 JF-NP-26 Chemical Structure

Further reading:


[1] Ellis-Davies GC. (2007). Caged compounds: photorelease technology for control of cellular chemistry and physiology. Nat Methods. 2007 Aug;4(8):619-28

[2] Mayer, G. and Heckel, A. (2006). Biologically Active Molecules with a “Light Switch”. Angewandte Chemie International Edition, 45: 4900-4921

[3] Paoletti P, Ellis-Davies GCR, Mourot A. (2019). Optical control of neuronal ion channels and receptors. Nat Rev Neurosci. 2019 Sep;20(9):514-532.