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Kumar A, Moody L, Olaivar JF, et al. Inhibition of Aβ42 peptide aggregation by a binuclear ruthenium(II)-platinum(II) complex: Potential for multi-metal organometallics as anti-amyloid agents. ACS Chem Neurosci. 2010;2010(10):691-701doi: 10.1021/cn100046m.
Kumar, A., Moody, L., Olaivar, J. F., Lewis, N. A., Khade, R. L., Holder, A. A., Zhang, Y., & Rangachari, V. (2010). Inhibition of Aβ42 peptide aggregation by a binuclear ruthenium(II)-platinum(II) complex: Potential for multi-metal organometallics as anti-amyloid agents. ACS chemical neuroscience, 2010(10), 691-701. https://doi.org/10.1021/cn100046m
Kumar, Amit, et al. "Inhibition of Aβ42 peptide aggregation by a binuclear ruthenium(II)-platinum(II) complex: Potential for multi-metal organometallics as anti-amyloid agents." ACS chemical neuroscience vol. 2010,10 (2010): 691-701. doi: https://doi.org/10.1021/cn100046m
Kumar A, Moody L, Olaivar JF, Lewis NA, Khade RL, Holder AA, Zhang Y, Rangachari V. Inhibition of Aβ42 peptide aggregation by a binuclear ruthenium(II)-platinum(II) complex: Potential for multi-metal organometallics as anti-amyloid agents. ACS Chem Neurosci. 2010 Aug 23;2010(10):691-701. doi: 10.1021/cn100046m. PMID: 21221412; PMCID: PMC3017353.
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ACS Chem Neurosci. 2010 Aug 23;2010(10):691-701. doi: 10.1021/cn100046m.

Inhibition of Aβ42 peptide aggregation by a binuclear ruthenium(II)-platinum(II) complex: Potential for multi-metal organometallics as anti-amyloid agents.

ACS chemical neuroscience

Amit Kumar, Lamaryet Moody, Jason F Olaivar, Nerissa A Lewis, Rahul L Khade, Alvin A Holder, Yong Zhang, Vijayaraghavan Rangachari

Affiliations

  1. Department of Chemistry and Biochemistry, University of Southern Mississippi, 118 College Dr # 5043, Hattiesburg, MS 39406, USA.

PMID: 21221412 PMCID: PMC3017353 DOI: 10.1021/cn100046m

Abstract

Design of inhibitors for amyloid-β (Aβ) peptide aggregation has been widely investigated over the years towards developing viable therapeutic agents for Alzheimer's disease (AD). The biggest challenge seems to be inhibiting Aβ aggregation at the early stages of aggregation possibly at the monomeric level, as 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 Pt(II) ([Pt(BPS)Cl(2)]) was reported to effectively inhibit Aβ42 aggregation and toxicity (1). 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 Pt(II) and Ru(II) that inhibited Aβ42 aggregation at an early stage of aggregation and seemed to have different modes of interaction than the previously reported Pt(II) 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 ligands, which will open doors to new rationale for Aβ inhibition.

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