Journal
ANALYTICAL CHEMISTRY
Volume 82, Issue 20, Pages 8558-8565Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ac101583q
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Funding
- Estonian Ministry of Education and Research [SF0140055s08]
- Estonian Science Foundation [9171, 6840]
- World Federation of Scientists
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Aggregation of amyloid-beta (A beta) 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 A beta 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 A beta derivatives. We have developed a label-free MALDI MS-based screening test for inhibitors of A beta(42) 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 A beta(42) fibrillization.
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