Active site modified protease .alpha.-1-antitrypsin inhibitors
AssigneeChiron Corporation
InventorsPhilip J. Barr, Robert A. Hallewell, Steven Rosenberg
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Abstract
Proteinaceous composition are provided which inhibit naturally occurring serine proteases. Particularly, an amino acid sequence analogous to human .alpha..sub.1 -antitrypsin is modified at the active site while maintaining protease inhibition. The methionine at the active site is substituted with an oxidatively stable amino acid, while other amino acids may also be changed, added or deleted, particularly at the termini. The yeast strains AB103.1 (pCl/PH05ATi(Val) and AB110 (pCl/1GAPATi(Val) were deposited at the A.T.C.C. on June 18, 1984 and given Accession Nos. 20711 and 20712, respectively.
Claims4
An analog of human alpha-1-antitrypsin wherein the amino acid corresponding to the methionine at position 358 of wild-type alpha-1-antitrypsin is substituted with an aliphatic amino acid, said analog exhibiting human leukocyte elastase activity and resistant to oxidation by N-chlorosuccinimide.
Dependencies are inferred from the claim text.