HaloTag Development

My research project is working with a HaloTags ligand and a variety of HaloTags receptors. What are HaloTags? The HaloTags ligand is customizable and but there are a few consistent features a base, a long flexible linker, and a halogen head at the end of the linker.  The base can be composed of a wide variety of compounds. It can be composed of aromatic rings that allow for detection of ligand binding, or it can be a drug that can spatially linker near its respective channel allowing for a faster uptake of the drug. The linker itself can be composed of different atoms, traditionally a long carbon chain. The linker is used as a tether to get the halogen head into the enzymatic pocket of the enzyme. The linker is a connector between the base and the halogen. The part that binds to the HaloTags receptor is a halogen at the end of the linker. The ligand’s halogen is attacked by a nucleophilic residue in the enzyme allowing the reaction to occur.

There are a few things that make this a great system. The first is that most eukaryotic systems do not have a mechanism to digest HaloTags ligands. This makes the HaloTag ligand binding specific as only HaloTags Ligands are only able to bind to the receptor. Another benefit of this system is that it can be differentiated into different cell types. The ability to differentiate between cell types allows for a better analysis of the effects pharmaceuticals have on a system of cells. The specificity of HaloTags also enables it to react in low concentrations allowing for ease of binding to a receptor for the pharmaceutical base.

What exactly am doing with HaloTags?  I am looking at a single ligand and then finding the receptor that binds onto that ligand the best. There is a wide variety of different ligands that have few different amino acid sequences. The strongest binding receptor over time is extracted and then sequenced.

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