ALZHEIMERS BETA-AMYLOID PEPTIDE - AFFINITY FOR METAL-CHELATES

Alzheimer's amyloid peptide, A beta(1-42) and its fragments, A beta(1- 28) and A beta(1-16), were chromatographed on IDA-M(II) columns (M: Cu 2+, Ni2+ and Zn2+). The retention of A beta(1-42) and its fragments on IDA-Cu(II) could not be reversed in decreasing a gradient of pH, from 7.0 to 4.0. All A beta peptides were recovered from IDA-Ni(II) column s in a decreasing pH gradient from 7.0 to 4.0, within the pH range fro m 5.6 to 5.1. A beta(1-42) peptide was strongly retained on IDA-Zn(II) at pH 4.0, but its A beta(1-28) and A beta(1-16) were only transientl y retained on IDA-Zn(II) columns when applied at pH 6.1. We submit tha t histidine clusters, residing both in the Alzheimer's beta-amyloid pe ptide and in most of the APP/APLP superfamily of proteins, constitute high-affinity binding sites for immobilized metal chelates. (C) Munksg aard 1998.