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
Patent
1989-03-01
1993-12-14
Moskowitz, Margaret
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, 435184, A61K 3702, C12N 1108
Patent
active
052704475
ABSTRACT:
A family of metalloproteinases exist which cleave extracellular matrix molecules. These metalloproteinases are secreted in a latent inactive form and require activation in order to specifically cleave the preferred substrate. A series of peptides have been prepared based on the complete sequence analysis of type IV Procollagenase. Peptide inhibitors were synthesized which correspond to cysteine repeat regions and histidine containing regions; the mechanism of action of these peptides involves inhibition of binding of the enzyme to the substrate. Peptide inhibitors were synthesized which correspond to the peptide cleaved off during activation, and constitute a novel class of metalloproteinase inhibitors. These inhibitors are members of a series of peptides which contain the core amino acid sequence PRCG. The cysteine residue is required for activity. Affinity purified antibodies directed against specific peptides can be used to a) detect any general metalloproteinase enzyme with the sequence in part VAAHE or PRCGNPD, and distinguish it from other known members of the metalloproteinase family, b) block functional domains resulting in the inhibition of enzyme activity, and c) distinguish latent from activated forms of the enzyme.
REFERENCES:
McKerrow, The Journal of Biological Chemistry, vol. 262, No. 13, May 5, 1987, p. 5943.
Fini, et al. Biochemistry 1987, 26, 6156-6165.
Article entitled "Molecular Cloning" A Laboratory Manual by T. Maniatis; E. F. Fritsch; J. Sambrook; Chapter 12 Vectors that Express Cloned DNA in Escherichia coli.
Krutzsch Henry
Liotta Lance A.
Stetler-Stevenson William
Benson Robert
Moskowitz Margaret
Sisson Bradley L.
The United States of America as represented by the Department of
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