Interaction of metal ions with the His13-His14 sequence relevant to Alzheimer's disease

The interaction of a series of metal ions (i.e., groups 1 and 2, first-row transition metals, and groups 11-14) with the His13-His14 sequence relevant to Alzheimer's disease has been studied using quantum chemical calculations. Metal ions prefer to occupy three coordination sites at two Nδ of the imidazole rings and one carbonyl oxygen. Simulated IR spectra reveal that vibrational frequency of C-O stretch affords a sensitive probe for understanding the interaction of His13-His14 with metal ions. The relative strength of the interaction of His13-His14 with the representative metal ions follows the order of K(+) < Ca(2+) < Zn(2+) < Cu(2+) < Fe(3+) < Al(3+), which is closely correlated with the available experimental results, providing a vivid physical picture about how metal ions bind to amyloid β-peptide. IR spectra of the [M·(His13-His14)](n+) complexes could be measured by infrared photodissociation spectroscopic technique and thus afford useful information for the understanding of structure-function relationship and the design of suitable drugs.