Inhibition of Aβ42 Peptide Aggregation by a Binuclear Ruthenium(II)−Platinum(II) Complex: Potential for Multimetal Organometallics as Anti-amyloid Agents
Chemistry and Biochemistry
Design of inhibitors for amyloid-β (Aβ) peptide aggregation has been widely investigated over the years toward developing viable therapeutic agents for Alzheimer’s disease (AD). The biggest challenge seems to be inhibiting Aβ aggregation at the early stages possibly at the monomeric level, because oligomers are known to be neurotoxic. In this regard, exploiting the metal-chelating property of Aβ to generate molecules that can overcome this impediment presents some promise. Recently, one such metal complex containing PtII ([Pt(BPS)Cl2]) was reported to effectively inhibit Aβ42 aggregation and toxicity (Barnham, et al. (2008) Proc. Natl. Acad. Sci. U.S.A.105, 6813). This complex was able bind to Aβ42 at the N-terminal part of the peptide and triggered a conformational change resulting in effective inhibition. In the current report, we have generated a mixed-binuclear metal complex containing PtII and RuII metal centers that inhibited Aβ42 aggregation at an early stage and seemed to have different modes of interaction than the previously reported PtII complex, suggesting an important role of the second metal center. This ‘proof-of-concept’ compound will help in developing more effective molecules against Aβ aggregation by modifying the two metal centers as well as their bridging ligands, which will open doors to new rationale for Aβ inhibition.
ACS Chemical Neuroscience
Olaivar, J. F.,
Lewis, N. A.,
Khade, R. L.,
Holder, A. A.,
(2010). Inhibition of Aβ42 Peptide Aggregation by a Binuclear Ruthenium(II)−Platinum(II) Complex: Potential for Multimetal Organometallics as Anti-amyloid Agents. ACS Chemical Neuroscience, 1(10), 691-701.
Available at: https://aquila.usm.edu/fac_pubs/8902