Investigation of the Noncovalent Interactions Between Anti-Amyloid Agents and Amyloid β Peptides by ESI-MS

This paper describes an efficient and reproducible screening method for identifying low molecular weight compounds that bind to amyloid beta peptides (A beta) peptides using electrospray ionization mass spectrometry (ESI-MS). Low molecular weight compounds capable of interacting with soluble A beta may be able to modulate/inhibit the A beta aggregation process and serve as potential disease-modifying agents for AD. The present approach was used to rank the binding affinity of a library of compounds to A beta 1-40 peptide. The results obtained show that low molecular weight compounds bind similarly to A beta 1-42, A beta 1-40, as well as A beta 1-28 peptides and they underline the critical role of A beta peptide charge motif in binding at physiological pH. Finally, some elements of structute-activity relationship (SAR) involved in the binding affinity of homotaurine to soluble A beta peptides are discussed. (J Am Soc Mass Spectrom 2010, 21, 1506-1514) (C) 2010 Published by Elsevier Inc. on behalf of American Society for Mass Spectrometry