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AssigneeVertex Pharmaceuticals Incorporated
InventorsRoy A. Black, Paul R. Sleath, Shirley R. Kronheim
Estimating the term…
There is disclosed an isolated polypeptide and derivatives thereof having protease biological activity for human precursor IL-1.beta. and for a substrate comprising: R.sub.1 -Asp-R.sub.2 -R.sub.3 wherein R.sub.1 and R.sub.3 are independently any D or L isomer amino acid, R.sub.2 is Ala or Gly, and wherein the specific protease cleavage site is between Asp and R.sub.2. Inhibitor compounds, compositions and methods for inhibiting Interleukin 1.beta. protease activity are also disclosed. The inhibitor compounds comprise an amino acid sequence of from 1 to about 5 amino acids having an N-terminal blocking group and a C-terminal Asp residue connected to an electronegative leaving group, wherein the amino acid sequence corresponds to the sequence Ala-Tyr-Val-His-Asp.
A compound comprising an amino acid sequence of from 1 to 4 amino acid residues having an N-terminal blocking group and a C-terminal Asp residue connected to an electronegative leaving group, wherein said amino acid sequence substantially corresponds to at least a portion of the sequence Ala-Tyr-Val-His-Asp, residues 112 to 116 of Seq. I.D. No. 3.
A pharmaceutical composition comprising a physiologically acceptable carrier and a compound of the formula:
A method of inhibiting IL-1.beta. protease activity in a mammal in need of such treatment comprising administering to said mammal an effective inhibitory amount of a compound of the formula:
A method of treating inflammation or treating an autoimmune disease in a mammal in need of such treatment comprising administering to said mammal an effective amount of a compound of the formula:
A compound selected from the group consisting of Boc-Asp-CH.sub.2 F, Boc-His-Asp-CH.sub.2 F, Boc-Phe-Asp-CH.sub.2 F, Boc-Pro-Asp-CH.sub.2 F, Boc-Tyr-Asp-CH.sub.2 F, Ac-His-Asp-CH.sub.2 F, Ac-Phe-Asp-CH.sub.2 F, Ac-Pro-Asp-CH.sub.2 F, Ac-Tyr-Asp-CH.sub.2 F, Cb.sub.3 -His-Asp-CH.sub.2 F, Cb.sub.3 -Phe-Asp-CH.sub.2 F, Cb.sub.3 -Pro-Asp-CH.sub.2 F, and Cb.sub.3 -Tyr-Asp-CH.sub.2 F wherein Boc is t-butoxycarbonyl, Ac is acetyl and Cb.sub.3 is benzyloxycarbonyl.
Dependencies are inferred from the claim text.