Abstract: A class of cysteine protease inhibitors which inactivate a cysteine protease by covalently bonding to the protease and releasing a heterocyclic leaving group is presented. The cysteine protease inhibitors of the present invention comprise a first portion which targets a desired cysteine protease and positions the inhibitor near the thiolate anion portion of the active site of the protease, and a second portion which covalently bonds to the cysteine protease and irreversibly deactivates that protease by providing a carbonyl or carbonyl-equivalent which is attacked by the thiolate anion of the active site of the cysteine protease to sequentially cleave a heterocyclic leaving group. The heterocyclic leaving group of the protease inhibitor is of the formula: —O—Het, where Het is a heterocycle having 4-7 atoms in the ring, with at least one of the heterocycle atoms being N, O or S.

Abstract: Cysteine protease inhibitors which deactivate the protease by covalently bonding to the cysteine protease and releasing the enolate of a 1,3-dicarbonyl (or its enolic form). The cysteine protease inhibitors of the present invention accordingly comprise a first portion which targets a desired cysteine protease and positions the inhibitor near the thiolate anion portion of the active site of the protease, and a second portion which covalently bonds to the cysteine protease and irreversibly deactivates that protease by providing a carbonyl or carbonyl-equivalent which is attacked by the thiolate anion of the active site of the cysteine protease to sequentially cleave a .beta.-dicarbonyl enol ether leaving group.

Abstract: A class of cysteine protease inhibitors which inactivate a cysteine protease by covalently bonding to the protease and releasing a heterocyclic leaving group is presented. The cysteine protease inhibitors of the present invention comprise a first portion which targets a desired cysteine protease and positions the inhibitor near the thiolate anion portion of the active site of the protease, and a second portion which covalently bonds to the cysteine protease and irreversibly deactivates that protease by providing a carbonyl or carbonyl-equivalent which is attacked by the thiolate anion of the active site of the cysteine protease to sequentially cleave a heterocyclic leaving group. The heterocyclic leaving group of the protease inhibitor is of the formula: --O--Het, where Het is a heterocycle having 4-7 atoms in the ring, with at least one of the heterocycle atoms being N, O or S.

Abstract: Cysteine protease inhibitors which deactivate the protease by covalently bonding to the cysteine protease and releasing the enolate of a 1,3-dicarbonyl (or its enolic form). The cysteine protease inhibitors of the present invention accordingly comprise a first portion which targets a desired cysteine protease and positions the inhibitor near the thiolate anion portion of the active site of the protease, and a second portion which covalently bonds to the cysteine protease and irreversibly deactivates that protease by providing a carbonyl or carbonyl-equivalent which is attacked by the thiolate anion of the active site of the cysteine protease to sequentially cleave a .beta.-dicarbonyl enol ether leaving group.

Abstract: A class of cysteine protease inhibitors which inactivate a cysteine protease by covalently bonding to the protease and releasing a heterocyclic leaving group is presented. The cysteine protease inhibitors of the present invention comprise a first portion which targets a desired cysteine protease and positions the inhibitor near the thiolate anion portion of the active site of the protease, and a second portion which covalently bonds to the cysteine protease and irreversibly deactivates that protease by providing a carbonyl or carbonyl-equivalent which is attacked by the thiolate anion of the active site of the cysteine protease to sequentially cleave a heterocyclic leaving group. The heterocyclic leaving group of the protease inhibitor is of the formula: --O--Het, where Het is a heterocycle having 4-7 atoms in the ring, with at least one of the heterocycle atoms being N, O or S.

Abstract: A class of cysteine protease inhibitors which inactivate a cysteine protease by covalently bonding to the protease and releasing a heterocyclic leaving group is presented. The cysteine protease inhibitors of the present invention comprise a first portion which targets a desired cysteine protease and positions the inhibitor near the thiolate anion portion of the active site of the protease, and a second portion which covalently bonds to the cysteine protease and irreversibly deactivates that protease by providing a carbonyl or carbonyl-equivalent which is attacked by the thiolate anion of the active site of the cysteine protease to sequentially cleave a heterocyclic leaving group. The heterocyclic leaving group of the protease inhibitor is of the formula: --O-- Het, where Het is a heterocycle having 4-7 atoms in the ring, with at least one of the heterocycle atoms being N, O or S.

Abstract: A method of treating medical conditions with proteinase inhibitors of the formula: ##STR1## wherein B is H or an amino acid blocking group for the N-terminal amino acid nitrogen;R.sub.1 is an optionally protected .alpha.-amino acid side chain such that P.sub.2 is the residue of an .alpha.-amino acid selected from the group consisting of phenylalanine (Phe), leucine (Leu), tyrosine (Tyr) and valine (Val), and substituted analogs thereof, particularly including Tyr(OMe);R.sub.2 is an optionally protected .alpha.-amino acid side chain such that P.sub.1 is the residue of an .alpha.

Abstract: The preparation of magnesium benzyl fluoromalonate and other equivalent materials, the synthetic equivalents of the --CH.sub.2 F moiety, is described. Reaction between these reagents and the in situ-formed imidazolides of various carboxylic acids gives beta-keto-alpha-fluoroesters, which upon hydrogenation and spontaneous decarboxylation yields fluoromethyl ketones in excellent yields. The overall transformation from RCOOH to RCOCH.sub.2 F is thus illustrated.

Abstract: The preparation of magnesium benzyl fluoromalonate and other equivalent materials, the synthetic equivalents of the --CH.sub.2 F moiety, is described. Reaction between these reagents and the in situ-formed imidazolides of various carboxylic acids gives beta-keto-alpha-fluoroesters, which upon hydrogenation and spontaneous decarboxylation yields fluoromethyl ketones in excellent yields. The overall transformation from RCOOH to RCOCH.sub.2 F is thus illustrated.

Abstract: The preparation of magnesium benzyl fluoromalonate and other equivalent materials, the synthetic equivalents of the --CH.sub.2 F moiety, is described. Reaction between these reagents and the in situ-formed imidazolides of various carboxylic acids gives beta-keto-alpha-fluoroesters, which upon hydrogenation and spontaneous decarboxylation yields fluoromethyl ketones in excellent yields. The overall transformation from RCOOH to RCOCH.sub.2 F is thus illustrated.

Abstract: Peptide thioneamides are provided as synthetic substrates for cysteine proteases. The compounds of the invention are peptides consisting of one or more blocked or unblocked amino acids wherein the terminal carboxy of the peptides are thionated and forms a thioneamide linkage with a fluorogenic or chromogenic leaving group. The alpha carbonyls of the remaining amino acids are thionated or unthionated. The invention includes methods and kits for using the peptide thioneamides.