Xin, Bo-Tao published the artcileStructure-based design of inhibitors selective for human proteasome β2c or β2i subunits, Safety of (S)-2-Methylpropane-2-sulfinamide, the main research area is proteasome beta 2c 2i subunit inhibitor crystal structure.
Subunit-selective proteasome inhibitors are valuable tools to assess the biol. and medicinal relevance of individual proteasome active sites. Whereas the inhibitors for the β1c, β1i, β5c, and β5i subunits exploit the differences in the substrate-binding channels identified by X-ray crystallog., compounds selectively targeting β2c or β2i could not yet be rationally designed because of the high structural similarity of these two subunits. Here, we report the development, chem. synthesis, and biol. screening of a compound library that led to the identification of the β2c- and β2i-selective compounds LU-002c (4 (I); IC50 β2c: 8 nM, IC50 β2i/β2c: 40-fold) and LU-002i (5 (II); IC50 β2i: 220 nM, IC50 β2c/β2i: 45-fold), resp. Co-crystal structures with β2 humanized yeast proteasomes visualize protein-ligand interactions crucial for subunit specificity. Altogether, organic syntheses, activity-based protein profiling, yeast mutagenesis, and structural biol. allowed us to decipher significant differences of β2 substrate-binding channels and to complete the set of subunit-selective proteasome inhibitors.
Journal of Medicinal Chemistry published new progress about Crystal structure. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, Safety of (S)-2-Methylpropane-2-sulfinamide.
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics