Title
NMR and CD studies on the interaction of Alzheimer β-amyloid peptide (12–28) with β-cyclodextrin
Author
Xu-rong Qin, Hiroshi Abe, Hiroshi Nakanishi
Year
2002
Journal
Biochemical and Biophysical Research Communications
Abstract
Polymerization of the amyloid β-peptide (Aβ) has been identified as a major feature of the pathogenesis of Alzheimer’s disease (AD). Inhibition of the formation of these toxic polymers of Aβ has emerged as an approach for developing therapeutics for AD. NMR and CD spectra were used to investigate the interaction between cyclodextrin and Aβ(12–28) peptide, which was reported to be an important region for forming amyloid fibrils. CD spectral analyses show that of the α-, β- and γ-cyclodextrins only β-cyclodextrin inhibits the aggregation of Aβ(12–28) at pH 5.0. Analysis of the one-dimensional proton NMR spectra of Aβ(12–28) and the mixture of Aβ(12–28) with β-cyclodextrin clearly indicates that there are chemical shift changes in the aromatic ring of Phe19 and the methyl groups of Val18 in the peptide. The NOESY spectra show cross-peaks between H-3 and H-5 of β-cyclodextrin and the aromatic protons of Phe19 and Phe20. These chemical shift differences and NOEs demonstrate that there is an interaction between Aβ(12–28) and β-cyclodextrin. Analysis of the cross-peak intensity in the NOESY spectra reveals that the aromatic rings of Phe19 and 20 are generally inserted into β-cyclodextrin at the broad side and are oriented toward the narrow side of the cavity.
Instrument
J-720
Keywords
Circular dichroism, Secondary structure, Ligand binding, Biochemistry