STABILIZATION OF SECONDARY STRUCTURE OF ALZHEIMER P-PROTEIN BY ALUMINUM(III) IONS AND D-ASP SUBSTITUTIONS

The CD spectra of the D-Asp substituted analogs of amyloid peptides, beta 6-25 and beta 1-40, showed a distinct blue-shift on A1(3+) complexation. The influence of Al3+ coordination was most significant on the triply substituted beta 1-40 (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 beta 1-40. These observations suggest that Al3+ interaction with D-Asp induces the peptide backbone to increase its antiparallel beta-sheet character. D-Asp substitution and chelation by A(l3+) lead to increased stability of higher molecular weight species of beta 1-40, and thereby could increase the toxicity of the Alzheimer amyloid protein. (C) 1995 Academic Press, Inc.