title: 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.
abstract: The reaction of the ruthenium(II) complex fac-[Ru(CO)(3)Cl(2)(N(1)-thz)] (I hereafter; thz = 1,3-thiazole) with human beta-amyloid peptide 1-28 (Abeta(28)) and the resulting {Ru(CO)(3)}(2+) peptide adduct was investigated by a variety of biophysical methods. (1)H NMR titrations highlighted a selective interaction of {Ru(CO)(3)}(2+) with Abeta(28) histidine residues; circular dichroism revealed the occurrence of a substantial conformational rearrangement of Abeta(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 Abeta(42). The implications of the above findings for a possible use of ruthenium compounds in Alzheimer's disease are discussed.
authors.affiliation: Department of Chemistry, University of Siena, Via A. Moro, 53100 Siena, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Valensin
authors.forename: Paolo
authors.initials: P
authors.lastname: Anzini
authors.forename: Elena
authors.initials: E
authors.lastname: Gaggelli
authors.forename: Nicola
authors.initials: N
authors.lastname: Gaggelli
authors.forename: Gabriella
authors.initials: G
authors.lastname: Tamasi
authors.forename: Renzo
authors.initials: R
authors.lastname: Cini
authors.forename: Chiara
authors.initials: C
authors.lastname: Gabbiani
authors.forename: Elena
authors.initials: E
authors.lastname: Michelucci
authors.forename: Luigi
authors.initials: L
authors.lastname: Messori
authors.forename: Henryk
authors.initials: H
authors.lastname: Kozlowski
authors.forename: Gianni
authors.initials: G
authors.lastname: Valensin
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002942:Circular Dichroism; D015195:Drug Design; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D010446:Peptide Fragments / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D016229:Amyloid beta-Peptides; D009942:Organometallic Compounds; D010446:Peptide Fragments; C084358:amyloid beta-protein (1-28); D006639:Histidine; D012428:Ruthenium