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Oligomerization Alters Binding Affinity Between Amyloid Beta and a Modulator of Peptide Aggregation.
Hilt, Silvia; Rojalin, Tatu; Viitala, Tapani; Koivuniemi, Artturi; Bunker, Alex; Hogiu, Sebastian Wachsmann; Kálai, Tamás; Hideg, Kálmán; Yliperttula, Marjo; Voss, John C.
Afiliación
  • Hilt S; Department of Biochemistry & Molecular Medicine, University of California, Davis, CA 95616, USA.
  • Rojalin T; Department of Pathology and Laboratory Medicine, and Center for Biophotonics, University of California Davis, USA.
  • Viitala T; Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Finland.
  • Koivuniemi A; Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Finland.
  • Bunker A; Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Finland.
  • Hogiu SW; Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki, Finland.
  • Kálai T; Department of Pathology and Laboratory Medicine, and Center for Biophotonics, University of California Davis, USA.
  • Hideg K; Intellectual Ventures/Global Good, Bellevue, WA, USA.
  • Yliperttula M; Institute of Organic and Medicinal Chemistry, University of Pécs, H 7624 Pécs, Szigeti st. 12. Pécs, Hungary.
  • Voss JC; Institute of Organic and Medicinal Chemistry, University of Pécs, H 7624 Pécs, Szigeti st. 12. Pécs, Hungary.
J Phys Chem C Nanomater Interfaces ; 121(43): 23974-23987, 2017 Nov 02.
Article en En | MEDLINE | ID: mdl-30214656
The soluble oligomeric form of the amyloid beta (Aß) 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 Aß. Here we introduce the multi-parametric surface plasmon resonance (MP-SPR) approach to quantify SLF binding and effect on the self-association of the peptide via a label-free, real-time approach. Kinetic analysis of SLF binding to Aß and measurements of layer thickness alterations inform on the mechanism underlying the ability of SLF to inhibit Aß toxicity and its progression towards larger oligomeric assemblies. Depending on the oligomeric state of Aß, distinct binding affinities for SLF are revealed. The Aß monomer and dimer uniquely possess sub-nanomolar affinity for SLF via a non-specific mode of binding. SLF binding is weaker in oligomeric Aß, 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 Aß peptide. The MP-SPR results together with in silico modeling provide affinity data for the SLF-Aß interaction and allow us to develop a new general method for examining protein aggregation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Phys Chem C Nanomater Interfaces Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Phys Chem C Nanomater Interfaces Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos