Woo Keun Kim

US Patent:

20070077552, Apr 5, 2007

Filed:

Oct 3, 2006

Appl. No.:

11/542564

Inventors:

Michael Hecht - Highland Park NJ, US
Woo Kim - Princeton NJ, US
Christine Wurth - Loerrach, DE

International Classification:

C12Q 1/04
C12Q 1/00

US Classification:

435004000, 435034000

Abstract:

We have developed a high through-put screen capable of isolating inhibitors of polypeptide aggregation, such as Alzheimer's Disease polypeptide Aβ aggregation, or other disease state aggregating proteins, from amidst large libraries of candidate inhibitors. The screen uses a fusion of a polypeptide domain that self-aggregates, such as an Aβ42 domain characteristic of Alzheimer's disease plaques, to a reporter construct, such as Green Fluorescent Protein (GFP) or similar fluorescent protein. In the absence of inhibition, the rapid misfolding and aggregation of Aβ42 causes the entire fusion protein to misfold, thereby preventing fluorescence. Compounds that inhibit Aβ42 aggregation enable GFP to fold into its native structure, and can be identified by the resulting fluorescent signal.