Protein degrader builiding block Pomalidomide-C
6-PEG
1-C
3-PEG
1-Butyl Iodide enables the synthesis of molecules for
targeted protein degradation and
PROTAC (proteolysis-targeting chimeras) technology. This conjugate contains a Cereblon (CRBN)-recruiting ligand, a linker with both hydrophobic and hydrophilic moieties, and a pendant iodoalkane for reactivity with a nucleophilic group on a target ligand. Because even slight alterations in ligands and crosslinkers can affect ternary complex formation between the target, E3 ligase, and PROTAC, many analogs are prepared to screen for optimal target degradation.
When used with other protein degrader building blocks with a pendant iodo group, parallel synthesis can be used to more quickly generate PROTAC libraries that feature variation in crosslinker length, composition, and E3 ligase ligand.