Using Covalent Labeling and Mass Spectrometry To Study Protein Binding Sites of Amyloid Inhibiting Molecules.

ABSTRACT: Amyloid aggregates are associated with several debilitating diseases, and there are numerous efforts to develop small molecule treatments against these diseases. One challenge associated with these efforts is determining protein binding site information for potential therapeutics because amyloid-forming proteins rapidly form oligomers and aggregates, making traditional protein structural analysis techniques challenging. Using β-2-microglobulin (β2m) as a model amyloid-forming protein along with two recently identified small molecule amyloid inhibitors (i.e., rifamycin SV and doxycycline), we demonstrate that covalent labeling and mass spectrometry (MS) can be used to map small-molecule binding sites for a rapidly aggregating protein. Specifically, three different covalent labeling reagents

SUBMITTER: Liu T 

PROVIDER: S-EPMC5677544 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature