University of Pennsylvania

The Trustees of the University of Pennylsvania

Norman Schechter

Harvey Rubin

Barry S Cooperman

Zhi M Wang

Michael Plotnick

Jeffrey Winkler

Takahiro Yano

Sacha Kassovska-Bratinova

Jiah Shin Teh

The present invention includes a method of treating or preventing a disease or disorder such as a mycobacterial infection, a Gram-positive bacterium infection, a yeast infection, an inflammatory condition, an auto-immune disorder and/or a proliferative disorder in a subject in need thereof. The method comprises administering to the subject a therapeutically effective amount of at least one compound of the invention, which includes clofazimine derivatives.

Therapeutic agents

A method of producing a recombinant serine protease inhibitor capable of effectively modulating serine protease activity is provided. Compositions capable of modulating serine protease activity and use of such compositions to regulate inflammatory processes in cells are also provided.

Methods for detecting genetic mutations resulting in protease inhibitor

The invention provides analogues of .alpha.-1-antichymotrypsin having amino acid substitutions at position 358. .alpha.-1-antichymotrypsin analogues having amino acid substitutions at positions 356-361 and analogues having amino acid substitutions at positions 356-361 wherein the amino acid at position 358 is substituted are also within the scope of the invention. These analogues exhibit chymase inhibitory activity. Also provided are novel .alpha.-1-antichymotrypsins having an N-terminal extension of methionine-alanine-serine or alanine-serine. Expression vectors for the production of .alpha.-1-antichymotrypsins are also provided. The present invention also provides host cells and cell cultures capable of expressing analogues of .alpha.-1-antichymotrypsin, as well as protein preparations from the host cells. Methods of producing and using the analogues of .alpha.-1-antichymotrypsin to inhibit chymase activity are also provided.

.alpha.-1-antichymotrypsin analogues having chymase inhibiting activity

The present invention provides an analogue of human .alpha.-1-antichymotrypsin wherein the amino acid at position 358 is selected from the group consisting of isoleucine, valine, alanine, aspattic acid, threonine, and glutamic acid.

.alpha.-1-antichymotrypsin analogues having elastase inhibitory activity

Methods of producing effective recombinant serine protease inhibitors

The invention provides .alpha.-1-antichymotrypsin and protein preparations comprising human .alpha.-1-antichymotrypsin produced by E. coli cells transformed with a DNA sequence encoding human .alpha.-1-antichymotrypsin. The invention also provides methods for producing .alpha.-1-antichymotrypsin. The invention further provides analogues of .alpha.-1-antichymotrypsin that exhibit antichymotrypsin, anti-trypsin and anti-thrombin activity and methods of producing the analogues.

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Philadelphia, PA, United States of America

Norman Schechter