Proteasome inhibition by peptide-semicarbazones

Peptide-semicarbazones derived from Z-Trp-Trp-Phe-aldehyde inhibit the chymotryptic activity of the human proteasome at nanomolar concentrations, but are less active in a NFκB reporter gene assay. Cyclic semicarbazones, in contrast, combine a strong inhibitory effect on the enzyme with an inhibition of NFκB signaling in the nanomolar range. In addition, a practical synthesis for scale-up of such compounds was developed.

Z-Trp-Trp-Phe-cyclic semicarbazone peptides inhibit the chymotryptic activity of the human proteasome at nanomolar concentrations.Figure optionsDownload as PowerPoint slide