title: Identification of [PtCl2(phen)] binding modes in amyloid-β peptide and the mechanism of aggregation inhibition.
abstract: Platinum phenanthroline complexes inhibit amyloid-β (Aβ) aggregation and reduce Aβ-caused neurotoxicity [Proc. Natl. Acad. Sci., 2008, 105, 6813-6818]. In this study, we investigated the interactions of Aβ(1-16) with [PtCl(2)(phen)] (phen=1,10-phenanthroline) using HPLC, ESI-MS, and NMR spectroscopy , and characterized the identity of products using tandem mass spectrometry. Results indicated that the phenanthroline ligand could induce noncovalent interactions between Aβ peptide and platinum complexes, leading to rapid Aβ platination. Multiple products were generated in the reaction, in which His6/His14 chelation was preferentially formed. Coordination of Asp7, His13, and Lys16 was also detected in other products. The majority of products were monoplatinated adducts with binding of the {Pt(phen)} scaffold, which impeded intermolecular interactions between Aβ peptides. Moreover, noncovalent interactions were confirmed by the interaction between Aβ peptide and [Pt(phen)(2)]Cl(2). The synergistic roles of the phen ligand and platinum(II) atom in the inhibition of Aβ aggregation are discussed.
authors: Department of Chemistry, CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, P.R. China.
authors: Guolin
authors: G
authors: Ma
authors: Fan
authors: F
authors: Huang
authors: Xuewei
authors: X
authors: Pu
authors: Liangyuan
authors: L
authors: Jia
authors: Tao
authors: T
authors: Jiang
authors: Lianzhi
authors: L
authors: Li
authors: Yangzhong
authors: Y
authors: Liu
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D003300:Copper / Q000737:chemistry*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009944:Organoplatinum Compounds / Q000737:chemistry*; D010618:Phenanthrolines / Q000737:chemistry*; D010984:Platinum / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D016229:Amyloid beta-Peptides; D008024:Ligands; D009944:Organoplatinum Compounds; D010618:Phenanthrolines; D010984:Platinum; D003300:Copper; C025205:1,10-phenanthroline