Label-Free High-Throughput Screening Assay for Inhibitors of Alzheimer’s Amyloid-β Peptide Aggregation Based on MALDI MS

• Published in: Analytical chemistry (Washington) Vol. 82; no. 20; pp. 8558 - 8565
• Main Authors: Zovo, Kairit, Helk, Eneken, Karafin, Ann, Tõugu, Vello, Palumaa, Peep
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 15.10.2010
• Subjects: Amyloid beta-Peptides - analysis; Analytical chemistry; Chemistry; Exact sciences and technology; Kinetics; Peptide Fragments - analysis; Spectrometric and optical methods; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods; Chemical analysis; Peptides; Alzheimer disease; Suppression; Fluorescence; Matrix assisted laser desorption ionization; Screening test; Fluorescence spectrometry; Aggregation; Molecules; High speed; Speed; Automation; False positive; Interference; Method; In vitro; Screening; Sensitivity; Transmission electron microscopy; Fluorescent labelling; Strategy; Inhibitor; Library; Application; Mass spectrometry
• ISSN: 0003-2700; 1520-6882
• DOI: 10.1021/ac101583q

Aggregation of amyloid-β (Aβ) peptides is causatively linked to Alzheimer’s disease (AD); thus, suppression of this process by small molecule inhibitors is a widely accepted therapeutic and preventive strategy for AD. Screening of the inhibitors of Aβ aggregation deserves much attention; however, despite intensive efforts, there are only a few high-throughput screening methods available, all of them having drawbacks related to the application of external fluorescent probes or artificial Aβ derivatives. We have developed a label-free MALDI MS-based screening test for inhibitors of Aβ42 fibrillization that exhibits high sensitivity, speed, and automation possibilities suitable for high-throughput screening. The test was evaluated by transmission electron microscopy and compared with a fluorimetric thioflavin-based assay, where interference of a number of tested compounds with thioflavin T binding and/or fluorescence caused false-positive results. The MALDI MS-based method can significantly speed up in vitro screening of compound libraries for inhibitors of Aβ42 fibrillization.