Transient small molecule interactions kinetically modulate amyloid beta peptide self-assembly
2012 (English)In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 586, no 22, 3991-3995 p.Article in journal (Refereed) Published
Small organic molecules, like Congo red and lacmoid, have been shown to modulate the self-assembly of the amyloid beta peptide (A beta). Here, we show that A beta 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 A beta is in the co-aggregate. These weak transient interactions kinetically redirect the aggregation prone A beta from self-assembling into amyloid fibrils. These findings suggest that even such weak binders might be effective as therapeutics against pathogenic protein aggregation.
Place, publisher, year, edition, pages
2012. Vol. 586, no 22, 3991-3995 p.
Amyloid, Alzheimer's disease, NMR relaxation dispersion, Dynamic exchange
Biochemistry and Molecular Biology
Research subject Biophysics
IdentifiersURN: urn:nbn:se:su:diva-83815DOI: 10.1016/j.febslet.2012.09.035ISI: 000310783800010OAI: oai:DiVA.org:su-83815DiVA: diva2:577121