Synthetic inhibitors of the multicatalytic proteinase complex (proteasome).
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.
Wilk
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Department of Pharmacology, Mount Sinai School of Medicine, City University of New York, N.Y. 10029.
Figueiredo-Pereira
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D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002918:Chymotrypsin / Q000378:metabolism; D003374:Coumarins / Q000737:chemistry; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex; D013379:Substrate Specificity; D014452:Ubiquitins / Q000378:metabolism
D003374:Coumarins; D015853:Cysteine Proteinase Inhibitors; D009097:Multienzyme Complexes; D009842:Oligopeptides; D014452:Ubiquitins; C090535:benzyloxycarbonyl-isoleucyl-glutamyl(O-tert-butyl)-alanyl-leucinal; C046582:succinyl-leucyl-leucyl-valyl-tyrosyl-methylcoumarinamide; D002918:Chymotrypsin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex