TMP-HTag

Trimethoprim-Halotag (TMP-HTag) is a small molecule chemical linker developed for the rapid and reversible control of protein localization in living cells (Ballister). TMP is an dihydrofolate reductase (DHFR) inhibitor chosen for its specificity in binding to the bacterial form of DHFR.^[1][2] The other half of the linker is a Halotag, a self labelling bacterial globular protein ligand that can bind covalently and irreversibly to the chloroalkane group of a Haloenzyme.^[2][3] Positioned between the TMP group and HaloTag is a flexible linker that can be modified to optimize protein linking efficiency.^[2][3] The modular structure of TMP-HaloTag makes it an ideal heterobifunctional tool for use in chemically induced dimerization (CID).^[1][2] Additionally, TMP- HTag can be modified to include photo-cleavable groups that allow for the control of CID using light.^[1][2]