Investigation of the noncovalent interactions between anti-amyloid agents and amyloid beta 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 (Abeta) peptides using electrospray ionization mass spectrometry (ESI-MS). Low molecular weight compounds capable of interacting with soluble Abeta may be able to modulate/inhibit the Abeta 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 Abeta1-40 peptide. The results obtained show that low molecular weight compounds bind similarly to Abeta1-42, Abeta1-40, as well as Abeta1-28 peptides and they underline the critical role of Abeta peptide charge motif in binding at physiological pH. Finally, some elements of structure-activity relationship (SAR) involved in the binding affinity of homotaurine to soluble Abeta peptides are discussed.
Martineau
Eric
E
Chemistry Department, University of Ottawa, Ottawa, ON, Canada.
de Guzman
Janna M
JM
Rodionova
Lioudmila
L
Kong
Xianqi
X
Mayer
Paul M
PM
Aman
Ahmed M
AM
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D019151:Peptide Library; D011485:Protein Binding; D020539:Sequence Analysis, Protein; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013329:Structure-Activity Relationship; D013654:Taurine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use
D016229:Amyloid beta-Peptides; D019151:Peptide Library; D013654:Taurine; C001355:tramiprosate