Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 11 to 14 amino acid residues in defined sequence
Patent
1992-03-09
1994-05-31
Lee, Lester L.
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
11 to 14 amino acid residues in defined sequence
530331, 530330, 530329, 530328, C07K 500, C07K 700, A61K 3700
Patent
active
053170865
ABSTRACT:
Compounds are provided that are useful in inhibiting cysteine or serine proteinases. The compounds define a peptide backbone with a sulfur atom substituted in the backbone. A leaving group is associated, or bonded, to a carbon atom adjacent to the sulfur atom. The leaving group is displaceable either by hydrolysis under physiological conditions (with the hydrolyzed compound forming an aldehyde enzyme inhibitor) or by an active-site nucleophile of a cysteine or serine proteinase. When the leaving group is displaced by hydrolysis, then the compound functions as a protected derivative of the aldehyde functional group and is stabilized against oxidation or degradation, yet allows for release of the aldehyde moiety at the pharmacological site of action. The peptide sulfide analogues bearing a leaving group displaced by the active-site nucleophile covalently bond cysteine or serine proteinases and thus irreversibly inhibit these enzymes.
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Bartlett Paul A.
Mader Mary M.
Lee Lester L.
Salata Carol A.
The Regents of the University of California
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