Peptidyl vinyl sulphones: a new class of potent and selective cysteine protease inhibitors: S2P2 specificity of human cathepsin O2 in comparison with cathepsins S and L.

摘要: Peptidyl vinyl sulphones are a novel class of extremely potent and specific cysteine protease inhibitors. They highly active against the therapeutically important cathepsins O2, S L. The highest kinact/K1 values exceed 10(7)M(-1) x s(-1) for cathepsin 10(5)M(-1) O2 To study primary specificity site human effectiveness this inhibitors, series peptidyl with variations in P2 residue was synthesized. Leucine position proven to be most effective also Cathepsins share decreased accessibility towards hydrophobic non-branched residues such as aminohexanoic acid (norleucine), methionine oxidized methionine, but distinguished by their different affinity phenylalanine position. In contrast, accepts broader range its S2 subsite than specificity-determining pocket appears spatially more restricted those