Synthetic inhibitors of the multicatalytic proteinase complex (proteasome).

Abstract

Synthetic inhibitors of the multicatalytic proteinase complex (proteasome) can provide the means to uncover the functional significance and catalytic mechanism of this macromolecule. Although inhibitor development is still in its early stages, some useful compounds have already been prepared. Of the various types of inhibitors thus far studied, peptidyl aldehydes have been the most effective. Since peptidyl aldehydes inhibit both serine and cysteine proteinases, lack of specificity is their major limitation. The properties of one such compound N-benzyloxycarbonyl-IE(Ot-Bu)A-Leucinal, a potent inhibitor of suc-LLVY-MCA hydrolysis, are described in detail.