To develop a PROTAC molecule, the ligand of the protein of interest moiety should have .....

Question

A potency of inhibition higher than 1 uM.
A potency of inhibition lower than 1 uM.
An affinity towards the protein higher than 1 uM.
An affinity towards the protein lower than 1 uM.

Answer 1

To develop a PROTAC (Proteolysis Targeting Chimera) molecule, the ligand of the protein of interest moiety should have an affinity towards the protein lower than 1 µM.

This is because a higher affinity (lower Kd, typically under 1 µM) makes it more effective for the PROTAC to recruit the E3 ligase and facilitate the ubiquitination and subsequent degradation of the target protein. A lower binding affinity may not effectively promote the desired proteolytic action.