Abstract
The protease-binding sequence EAIPMSIPPE from α1-antitrypsin has been inserted into the cytokine interleykin-1β, replacing residues 50–53. The resulting mutant protein was cleaved specifically at a singly site by elastase and chymotrypsin, but not by trypson. The cleavage by elastase was shown to be between Met and Ser of the inserted loop. In contrast, wild-type interleukin is not sus-ceptible to cleavage by any of these enzymes. The mutant protein acts as an inhibitor of elastase, with a K1 of ∼30 μM. The wild type displays no such inhibitory actitvity. The overall structure of the mutant, as demonstrated byu CD, appears to be indistinguishabel from that fo the wild type. These results indicate that the protease-binding region fo α1-antitrypson can be recognized and is active even within the context of an entirely differentproteinstructure. Given that interleukinm-1β binds to, and is intenalized by, many types of cells, this hybrid protein also demonstrates the feasibility of using interleukin-1β as a delivery system for useful therapeutic agents.