NMR and CD studies on the interaction of Alzheimer <f>β</f>-amyloid peptide (12–28) with <f>β</f>-cyclodextrin

Polymerization of the amyloid <f>β</f>-peptide (A<f>β</f>) has been identified as a major feature of the pathogenesis of Alzheimer’s disease (AD). Inhibition of the formation of these toxic polymers of A<f>β</f> has emerged as an approach for developing therapeutics for AD. NMR and CD spectra were used to investigate the interaction between cyclodextrin and A<f>β</f>(12–28) peptide, which was reported to be an important region for forming amyloid fibrils. CD spectral analyses show that of the <f>α</f>-, <f>β</f>- and <f>γ</f>-cyclodextrins only <f>β</f>-cyclodextrin inhibits the aggregation of A<f>β</f>(12–28) at pH 5.0. Analysis of the one-dimensional proton NMR spectra of A<f>β</f>(12–28) and the mixture of A<f>β</f>(12–28) with <f>β</f>-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 <f>β</f>-cyclodextrin and the aromatic protons of Phe19 and Phe20. These chemical shift differences and NOEs demonstrate that there is an interaction between A<f>β</f>(12–28) and <f>β</f>-cyclodextrin. Analysis of the cross-peak intensity in the NOESY spectra reveals that the aromatic rings of Phe19 and 20 are generally inserted into <f>β</f>-cyclodextrin at the broad side and are oriented toward the narrow side of the cavity. [Copyright &y& Elsevier]