Anti-apoptotic compositions and methods using same
AssigneeThe Regents of the University of California
InventorsDale E. Bredesen, Celik Kayalar
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Abstract
The present invention provides methods and compositions for modulating the apoptotic activity of interleukin-1β converting enzyme (ICE). The present invention further provides methods and compositions for alleviating pathological conditions associated with apoptotic mechanisms.
Claims4
A method to identify compounds that modulate the apoptotic activity of ICE (interleukin-1β converting enzyme), said method comprising conducting a competitive binding assay employing ICE and a globular actin protein having at least one ICE cleavage site located in the P1 position relative to the cleavage site;
- wherein the ICE has an active site comprising an amino acid sequence as set forth in SEQ ID NO:1 and wherein a compound that reduces binding of the actin and the ICE is identified as modulating the apoptotic activity of ICE.
A bioassay for identifying compounds that modulate the apoptotic activity of ICE, said bioassay comprising:
- (a) contacting a mixture comprising
- i) a complex of DNase I and a globular actin polypeptide having at least one ICE cleavage site with an aspartyl residue located in the P1 position relative to the cleavage site, and
- ii) a test compound
- with an amount of ICE having an active site that comprises an amino acid sequence as set forth in SEQ ID NO:1, effective to cleave said actin polypeptide;
- and
- (b) identifying compounds that cause an increase of free DNase I in said mixture, wherein the increase of free DNase I indicates cleavage of the actin by the compound and diminished capacity of the ICE to inhibit DNase-induced apoptosis.
Dependencies are inferred from the claim text.