Identification of [PtCl2(phen)] binding modes in amyloid- peptide and the mechanism of aggregation inhibition. Academic Article uri icon

abstract

  • Platinum phenanthroline complexes inhibit amyloid- (A) aggregation and reduce A-caused neurotoxicity [Proc. Natl. Acad. Sci., 2008, 105, 6813-6818]. In this study, we investigated the interactions of A(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 A peptide and platinum complexes, leading to rapid A 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 A peptides. Moreover, noncovalent interactions were confirmed by the interaction between A peptide and [Pt(phen)(2)]Cl(2). The synergistic roles of the phen ligand and platinum(II) atom in the inhibition of A aggregation are discussed.

published proceedings

  • Chemistry

author list (cited authors)

  • Ma, G., Huang, F., Pu, X., Jia, L., Jiang, T., Li, L., & Liu, Y.

complete list of authors

  • Ma, Guolin||Huang, Fan||Pu, Xuewei||Jia, Liangyuan||Jiang, Tao||Li, Lianzhi||Liu, Yangzhong

publication date

  • October 2011

publisher