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CYLINDRINS AS ETIOLOGIC AGENTS OF AMYLOID DISEASES

United States Patent Application

20150307573
A1
View the Complete Application at the US Patent & Trademark Office
This invention relates, e.g., to a cylindrin, which is a non-covalent assembly of substantially identical chains of an amyloid or amyloid-related protein, which is a non-covalent assembly of substantially identical chains of an amyloid or amyloid-related protein, wherein each chain has a length of about 10-100 amino acid residues and comprises a single copy of a cylindrin-forming segment, or tandem adjacent copies of a cylindrin-forming segment, optionally separated by spacers, or adjacent copies of a first cylindrin-forming segment and a second complementary segment of the first cylindrin-forming segment, optionally separated by spacers, wherein at least about 2/3 of the amino acid residues in the chain are cylindrin-forming segments, wherein the cylindrin is a curved beta sheet formed from anti-parallel out-of-register extended protein strands, which is substantially filled with packed side chains. Also disclosed are methods for designing and making cylindrins, and methods for using them to identify inhibitors cylindrin-mediated cell toxicity.
Laganowsky, Arthur David (Los Angeles, CA), Eisenberg, David S. (Los Angeles, CA), Villarama, Rebecca Anne (Los Angeles, CA)
14/ 373,629
January 22, 2013
[0002] This invention was made with Government support under Grant No. AG029430 awarded by the National Institutes of Health, Grant No. 0445429, awarded by the National Science Foundation, and grant No. DE-ACO2-06CH11357, awarded by United States Department of Energy. The Government has certain rights in this invention.