Binding of Zn(II), Cu(II), and Fe(II) ions to Alzheimer's A beta peptide studied by fluorescence

Bioorg Med Chem Lett. 1999 Aug 2;9(15):2243-8. doi: 10.1016/s0960-894x(99)00357-1.

Abstract

Binding of Zn(II), Cu(II) and Fe(II) ions to A beta1-40, A beta1-42 and a single tryptophan mutant of Abeta 1-40 in solution at pH 7.4 was studied by fluorescent titration. Job plots and fitting of titration curves revealed formation of 1:1 and 1:2 peptide-metal complexes. For dimeric peptides A beta1-40 and A betaF4W the order of metal to peptide affinities is Fe < Cu > Zn, which is in agreement with the Irving-Williams series of complex stability. The affinity of A beta1-42 for Fe increases dramatically upon aggregation: K(D) changes from ca. 100 to ca. 0.2 microM.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism*
  • Binding, Competitive
  • Copper / metabolism*
  • Humans
  • Iron / metabolism*
  • Peptide Fragments / metabolism*
  • Spectrometry, Fluorescence
  • Zinc / metabolism*

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-43)
  • Copper
  • Iron
  • Zinc