Oligomerization Alters Binding Affinity between Amyloid Beta and a Modulator of Peptide Aggregation

Silvia Hilt, Tatu Rojalin, Tapani Viitala, Artturi Koivuniemi, Alex Bunker, Sebastian Wachsmann-Hogiu, Tamás Kálai, Kálmán Hideg, Marjo Yliperttula, John C. Voss*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

5 Citations (Scopus)


The soluble oligomeric form of the amyloid beta (Aβ) peptide is the major causative agent in the molecular pathogenesis of Alzheimer's disease (AD). We have previously developed a pyrroline-nitroxyl fluorene compound (SLF) that blocks the toxicity of Aβ. Here we introduce the multiparametric surface plasmon resonance (MP-SPR) approach to quantify SLF binding and its effect on the self-association of the peptide via a label-free, real-time approach. Kinetic analysis of SLF binding to Aβ and measurements of layer thickness alterations inform on the mechanism underlying the ability of SLF to inhibit Aβ toxicity and its progression toward larger oligomeric assemblies. Depending on the oligomeric state of Aβ, distinct binding affinities for SLF are revealed. The Aβ monomer and dimer uniquely possess subnanomolar affinity for SLF via a nonspecific mode of binding. SLF binding is weaker in oligomeric Aβ, which displays an affinity for SLF on the order of 100 μM. To complement these experiments we carried out molecular docking and molecular dynamics simulations to explore how SLF interacts with the Aβ peptide. The MP-SPR results together with in silico modeling provide affinity data for the SLF-Aβ interaction and allow us to develop a new general method for examining protein aggregation.

Original languageEnglish
Pages (from-to)23974-23987
Number of pages14
JournalJournal of Physical Chemistry C
Issue number43
Publication statusPublished - 2 Nov 2017
Externally publishedYes
MoE publication typeA1 Journal article-refereed


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