St. Jude Children's Research Hospital

Brian Bothner

Richard Kriwacki

William Lewis

The present invention discloses that the binding of Arf with Dm2, important components of the p53 tumor suppressor pathway, results in specific domains of both proteins undergoing a dramatic transition from dynamically disordered conformations to amyloid-like structures comprised of anti-parallel &#x3b2;-strands. The invention exploits this discovery by providing unique methods for identifying and/or designing compounds that mimic, inhibit and/or enhance the effect of Arf on Dm2. The present invention also provides specific peptides derived from the binding domains of Arf and Dm2 which co-assemble into supramolecular structures comprised of binary anti-parallel &#x3b2;-strands. The disclosed peptides may represent structural prototypes for a broader class of peptides that is capable of assembly into supramolecular structures.

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Bozeman, MT, United States of America

Brian Bothner