Brownsey, Duncan K. published the artcileIdentification of ligand linkage vectors for the development of p300/CBP degraders, HPLC of Formula: 343338-28-3, the main research area is protein CBP degrader development ligand linkage vector.
To develop new degrader mols. from an existing protein ligand a linkage vector must be identified and then joined with a suitable E3 ligase without disrupting binding to the resp. targets. This is typically achieved through empirically evaluating the degradation efficacy of a series of synthetic degraders. Our strategy for determining optimal linkage sites utilizes biotinylated protein ligands, linked via potential conjugation sites of an inhibitor to confirm whether target protein is maintained after forming a conjugate. This method provides low-cost, qual. evidence that the addition of a linker moiety at a specific position can be tolerated, guiding further optimization. We demonstrate the application of this method through the exploration of linkage vectors on A-485, a known ligand of p300/CBP, and found a conjugation site through a urea moiety. Pomalidomide was then conjugated through this site with several different linkers and cell viability and degradation were assessed for this library using a myeloma cell line, MM1. S. Compound 18i, with a PEG4 linker, was found to be the most effective p300 degrader and linker length greater than 10 atoms afforded enhanced degradation
RSC Medicinal Chemistry published new progress about Biodegradation. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, HPLC of Formula: 343338-28-3.
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics