Stabilization of Secondary Structure of Alzheimer β-Protein by Aluminum(III) Ions and D-Asp Substitutions

The CD spectra of the D-Asp substituted analogs of amyloid peptides, β6-25 and β1-40, showed a distinct blue-shift on A13+ complexation. The influence of Al3+ coordination was most significant on the triply substituted β1-40 (D-Asp 1,7,23). This analog showed a reduction of the minima near 210nm and a simultaneous increase in the maxima near 200nm as compared to the native L-Asp β1-40. These observations suggest that Al3+ interaction with D-Asp induces the peptide backbone to increase its antiparallel β-sheet character. D-Asp substitution and chelation by Al3+ lead to increased stability of higher molecular weight species of β1-40, and thereby could increase the toxicity of the Alzheimer amyloid protein.