Related Experiment Video
Updated: Apr 17, 2026

A11-positive β-amyloid Oligomer Preparation and Assessment Using Dot Blotting Analysis
Published on: May 22, 2018
Interaction of PiB-derivative metal complexes with beta-amyloid peptides: selective recognition of the aggregated
André F Martins1, David M Dias, Jean-François Morfin
1Centre de Biophysique Moléculaire, CNRS, Université d'Orléans, Rue Charles Sadron, 45071 Orléans Cedex 2 (France); Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Calçada Martim de Freitas, 3000-393 Coimbra (Portugal); Coimbra Chemistry Center, University of Coimbra, Rua Larga, 3004-535 Coimbra (Portugal); Present Address: Department of Chemistry, University of Texas at Dallas, Richardson, Texas 75083 (USA).
Abstract:
Metal complexes are increasingly explored as imaging probes in amyloid peptide related pathologies. We report the first detailed study on the mechanism of interaction between a metal complex and both the monomer and the aggregated form of Aβ1-40 peptide. We have studied lanthanide(III) chelates of two PiB-derivative ligands (PiB=Pittsburgh compound B), L(1) and L(2), differing in the length of the spacer between the metal-complexing DO3A macrocycle (DO3A=1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid) and the peptide-recognition PiB moiety. Surface plasmon resonance (SPR) and saturation transfer difference (STD) NMR spectroscopy revealed that they both bind to aggregated Aβ1-40 (KD =67-160 μM), primarily through the benzothiazole unit. HSQC NMR spectroscopy on the (15) N-labeled, monomer Aβ1-40 peptide indicates nonsignificant interaction with monomeric Aβ. Time-dependent circular dichroism (CD), dynamic light scattering (DLS), and TEM investigations of the secondary structure and of the aggregation of Aβ1-40 in the presence of increasing amounts of the metal complexes provide coherent data showing that, despite their structural similarity, the two complexes affect Aβ fibril formation distinctly. Whereas GdL(1), at higher concentrations, stabilizes β-sheets, GdL(2) prevents aggregation by promoting α-helical structures. These results give insight into the behavior of amyloid-targeted metal complexes in general and contribute to a more rational design of metal-based diagnostic and therapeutic agents for amyloid- associated pathologies.
More Related Videos
Related Concept Videos
Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid Fibrils
Metal-Ligand Bonds
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
Complexation Equilibria: The Chelate Effect
Complexation Equilibria: Factors Influencing Stability of Complexes

