Transient small molecule interactions kinetically modulate amyloid β peptide self-assembly.
Small organic molecules, like Congo red and lacmoid, have been shown to modulate the self-assembly of the amyloid β peptide (Aβ). Here, we show that Aβ forms NMR invisible non-toxic co-aggregates together with lacmoid as well as Congo red. We find that the interaction involves two distinct kinetic processes and at every given time point only a small fraction of Aβ is in the co-aggregate. These weak transient interactions kinetically redirect the aggregation prone Aβ from self-assembling into amyloid fibrils. These findings suggest that even such weak binders might be effective as therapeutics against pathogenic protein aggregation.
Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
Axel
A
Abelein
Lisa
L
Lang
Christofer
C
Lendel
Astrid
A
Gräslund
Jens
J
Danielsson
D000465:Algorithms; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003224:Congo Red / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D010078:Oxazines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D011487:Protein Conformation
D016229:Amyloid beta-Peptides; D010078:Oxazines; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C570487:lacmoid; D003224:Congo Red