Isotopic Dilution Provides No Evidence for Cu2 -Bridged β-Amyloid Homo-Oligomers

Abstract

The oligomerization of many peptides is known to be influenced by the binding of transition metal ions, with intermolecular metal–ion bridges being one possible mechanism. In the case of copper ions, it is possible to identify Cu2+ bridges between peptide monomers using EPR spectroscopy by analyzing the metal–ligand hyperfine structure in the spectra of a mixture of two peptides, each having the same amino acid sequence but a different isotopic content. This isotopic dilution method was previously used to show that the N-terminus of the misfolding peptide α-synuclein forms antiparallel Cu2+-bridged dimers, and such a quaternary structure was also proposed for the Cu2+-bound form of another m..