Optochemical Genetics

Background Info

Trans-membrane receptors allow a cell to communicate with its environment in response to a variety of input signals like changes in concentration of ligands (hormones / neuro transmitters), temperatures, pressure (acoustic waves / touch), trans membrane potential, or light intensity. In recent past, these sophisticated molecular machines can be reprogrammed to respond to unnatural input signals. 

Optochemical Genetics

About Optochemical Genetics

Optochemical Genetics is a new field of neuro-science, the activity of the neurons or other cell of interest is control, by targeting native photoreceptors using synthetically developed receptor molecules, as a result the sensitivity to a stimulus can be precisely located and also controlled. 

Application of Optochemical Genetics

Optogenetic molecules / photoreceptors that use light to control neurons can be used to highly targeted pain relief and might even restore sight to the blind. Synthetic molecules can be developed that can block the activity of pain-sensing neurons in a controlled and reversible way in a selective manner. 

Example: LIGHT SENSITIVE PAIN RELIEF –  Synthetized molecular – Quaternary ammonium-azobenzene-quaternary ammonium (QAQ) – selectively enter pain-sensing neutrons and its activity can be controlled by light. UV – turns it ON and sense PAIN; while GREEN light – turns it OFF and silences PAIN. 

Integration of synthetic photo-switches into mammalian receptor proteins has the unique advantage of enabling native signals to be optically controlled, thereby providing an additional ability to elucidate the physiological mechanisms by which the regulation of excitability and synaptic transmission controls circuits and behavior. 

Photosensitive Receptors 

  • CL – Caged Ligands – Simplest and Oldest approach- Ligand is endowed with a protecting group (Cage) that masks a functional group crucial to the ligand-receptor interaction and thus renders it ineffective. Cage protecting group, which can be toxic. 
  • PCL – Photo-chromic Ligands – Ligand carries a photo-switchable side-chain that can be switched between two / more configurations. It is not receptor-subtype selectivity and cellular targeting. 
  • PTL – Photo Switched tethered ligands – Ligand is covalently attached to its receptor in a site-directed manner through a tether that contains a photoswitch. 

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