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.

► Aβ and amyloid inhibitors form dynamic non-toxic co-aggregates.
► Aβ-lacmoid co-aggregates are low populated small sized generalized micelles.
► Weak transient interactions kinetically redirect Aβ from self-assembly.