fac-{Ru(CO)3}2+ selectively targets the histidine residues of the beta-amyloid peptide 1-28. Implications for new Alzheimer's disease treatments based on ruthenium complexes

The reaction of the ruthenium(II) complex fac-[Ru(CO)3Cl2(N1-thz)] (I hereafter; thz = 1,3-thiazole) with human ?-amyloid peptide 1-28 (A?28) and the resulting {Ru(CO)3}2+ peptide adduct was investigated by a variety of biophysical methods. 1H NMR titrations highlighted a selective interaction of {Ru(CO)3}2+ with A?28 histidine residues; circular dichroism revealed the occurrence of a substantial conformational rearrangement of A?28; electrospray ionization mass spectrometry (ESI-MS) suggested a prevalent 1:1 metal/peptide stoichiometry and disclosed the nature of peptide-bound metallic fragments. Notably, very similar ESI-MS results were obtained when I was reacted with A?42. The implications of the above findings for a possible use of ruthenium compounds in Alzheimer's disease are discussed.