fac-{Ru(CO)3}2+ Selectively Targets the Histidine Residues of the β-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 β-amyloid peptide 1-28 (Aβ28) 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 Aβ28 histidine residues; circular dichroism revealed the occurrence of a substantial conformational rearrangement of Aβ28; 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 Aβ42. The implications of the above findings for a possible use of ruthenium compounds in Alzheimer’s disease are discussed.