Designing azobenzene-based tools for controlling neurotransmission

• Published in: Current opinion in structural biology 2019-08, Vol.57, p.23-30
• Main Authors: Leippe, Philipp, Frank, James Allen
• Format: Article
• Language: English
• ISSN: 0959-440X; 1879-033X
• DOI: 10.1016/j.sbi.2019.01.022

[Display omitted] •Azobenzene photoswitches can be inserted into a ligand to enable optical control its target.•Photoswitching permits optical modulation of the ligand’s pharmacological and biophysical properties.•The spectral and kinetic properties of these photoswitchable drugs can be fine-tuned using synthetic chemistry.•When applied to target neuroreceptors, these probes enable reversible optical control of neurotransmission.•Tethering approaches allow for cell-specific genetic targeting in complex heterogeneous tissues such as the brain. Chemical and electrical signaling at the synapse is a dynamic process that is crucial to neurotransmission and pathology. Traditional pharmacotherapy has found countless applications in both academic labs and the clinic; however, diffusible drugs lack spatial and temporal precision when employed in heterogeneous tissues such as the brain. In the field of photopharmacology, chemical attachment of a synthetic photoswitch to a bioactive ligand allows cellular signaling to be controlled with light. Azobenzenes have remained the go-to photoswitch for biological applications due to their tunable photophysical properties, and can be leveraged to achieve reversible optical control of numerous receptors and ion channels. Here, we discuss the most recent advances in photopharmacology which will improve the use of azobenzene-based probes for neuroscience applications.