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Designed Amyloid β Peptide Fibril—A Tool for High‐Throughput Screening of Fibril Inhibitors
Author(s) -
Dolphin Gunnar T.,
Ouberai Myriam,
Dumy Pascal,
Garcia Julian
Publication year - 2007
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200700103
Subject(s) - fibril , amyloid fibril , peptide , chemistry , throughput , amyloid (mycology) , biophysics , high throughput screening , amyloid β , biochemistry , computer science , medicine , biology , disease , inorganic chemistry , telecommunications , wireless
Abstract Amyloid β peptide (Aβ) fibril formation is widely believed to be the causative event of Alzheimer’s disease pathogenesis. Therapeutic approaches are therefore in development that target various sites in the production and aggregation of Aβ. Herein we present a high‐throughput screening tool to generate novel hit compounds that block Aβ fibril formation. This tool is an application for our fibril model (Aβ 16–37 Y 20 K 22 K 24 ) 4 , which is a covalent assembly of four Aβ fragments. With this tool, screening studies are complete within one hour, as opposed to days with native Aβ 1–40 . A Z′ factor of 0.84±0.03 was determined for fibril formation and inhibition, followed by the reporter molecule thioflavin T. Herein we also describe the analysis of a broad range of reported inhibitors and non‐inhibitors of Aβ fibril formation to test the validity of the system.