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 N-delta 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+ < Ca2+ < Zn2+ < Cu2+ < Fe3+ < Al-3+,Al- which is closely correlated with the available experimental results, providing a vivid physical picture about how metal ions bind to amyloid beta-peptide. IR spectra of the [M center dot(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.