Compounds for inhibition of proteolysis

Details Compounds for inhibition of proteolysis Compounds for inhibition of proteolysis

1996-03-14

2000-01-18

MacMillan, Keith D.

Chemistry: natural resins or derivatives; peptides or proteins;

Peptides of 3 to 100 amino acid residues

15 to 23 amino acid residues in defined sequence

530330, 530331, 514 13, 514 18, A61K 3800, A61K 3804

Patent

active

060158778

ABSTRACT:
Compounds used to treat cancer which inhibit carboxy terminal proteolysis of proteins having a carboxyl-terminal -CAAX motif (C=cysteine, A=aliphatic amino acid, and X=any amino acid). The compounds have the formula W--Y--CH.sub.2 --Q, where:

REFERENCES:
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Ashby et al., "Endoproteolytic processing of a farnesylated peptide in vitro", Proc. Nat'l. Acad. Sci. USA, 89:4613-4617, 1992.
Chen et al., "Solubilization, Partial Purification, and Affinity Labeling of the Membrane-Bound Isoprenylated Protein Endoprotease", Biochemistry, 35:3227-3237, 1996.
Lai et al., "The .gamma. Subunit of transducin is farnesylated", Proc. Nat'l Acad. Sci. USA, 87:7673-7677, 1990.
Ma et al., "A microsomal endoprotease that specifically cleaves isoprenylated peptides", Proc. Nat'l. Acad. Sci. USA, 1992, pp. 6275-6279.
Ma et al., "Inhibitors of the Isoprenylated Protein Endoprotease", Biochemistry, 32:2386-2393, 1993.
Ma et al., "Mechanistic Studies on Human Platelet Isoprenylated Protein Methyltransferase: Farnesylcysteine Analogs Block Platelet Aggregation without inhibiting the Methyltransferase", Biochem. 33:5414-5420, 1994.
Perez-Sala et al., "Methylation and demethylation reactions of guanine nucleotide-binding proteins of retinal rod outer segments", Proc. Nat'l. Acad. Sci. USA, 88:3043-3046, 1991.

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