[3][4] Initially described by Kathleen Sakamoto, Craig Crews and Ray Deshaies in 2001,[5] the PROTAC technology has been applied by a number of drug discovery labs using various E3 ligases,[6] including pVHL,[7][8][9] CRBN,[10][11] Mdm2,[12] beta-TrCP1,[5] DCAF11,[13][14] DCAF15,[15] DCAF16,[15] RNF114,[15] and c-IAP1.
[21] PROTACs achieve degradation through "hijacking" the cell's ubiquitin–proteasome system (UPS) by bringing together the target protein and an E3 ligase.
[19] PROTACs take advantage of this cellular system by putting the protein of interest in close proximity to the E3 ligase to catalyze degradation.
[15] A hook effect is commonly observed with high concentrations of PROTACs due to the bifunctional nature of the degrader.
These BacPROTACs target the ClpC:ClpP protease system, an analogue with similar function to E3 ubiquitin ligase in bacterial cells.