Development of novel peptidomimetics containing a vinyl sulfone moiety as proteasome inhibitors.

摘要: Proteasome inhibition is a topic of great interest in anticancer research. The proteolytic activity this multicatalytic complex relies on three subunits, β1, β2 and β5, containing caspase-like, trypsin-like chymotrypsin-like active site, respectively. Several studies have demonstrated that, the activities, was most necessary for cell viability protein processing. Thus, efforts towards development proteasome inhibitors focused selective β5 subunit site. Herein, we report design synthesis series conformationally constrained tripeptidyl vinyl sulfones were determined to be good proteasome, with K(I) values sub-micromolar micromolar range. These compounds also tested against bovine pancreatic α-chymotrypsin human cathepsin B L, revealing selectivity target enzyme over these related enzymes.