Using Deuterium Exchange Electrospray Mass Spectrometry to Evaluate Inhibitors of Amyloid-beta Oligomerization

摘要

Misfolding and deposition of the amyloid beta (A(beta)) peptide into insoluble fibers in the brain is characteristic in Alzheimer's disease. Traditionally, the polymeric aggregates of fibrils of A(beta) are thought to be responsible for the development of the disease. More of recent studies, however, emphasize the highly neurotoxic nature of smaller oligomers. Efforts are focused on developing drugs that can delay, halt or possibly reverse this process. Development of analytical techniques to examine the extent of oligomerization has been especially challenging. A variety of mass spectrometric approaches have been applied, including the use of D/H X-ESI-MS to monitor oligomer formation. This approach takes advantage of the slower exchange of deuteriums that, upon oligomerization of the peptide, are hidden from interaction with the solvent.