Effects of New Ruthenium Amphiphile Compounds on Peptides Aggregation

Alzheimer's disease (AD) is a neurodegenerative disease with no certain cure, the most typical form of dementia. An ubiquitous observation in AD patients is the formation of plaques in their gray matter. 18 The dominant components of these plaques are peptides known as amyloid beta (A~). 1 b. 1 c In our studies, we applied a new ruthenium complex ([!J6-(C6H6)RuCIL]PF6, L = 2-(4-dodecyloxyphenyl)-5-(2-pyridyl)-1 ,3,4- oxadiazole; Rul, Figure lA) as an A~ aggregation inhibitor and disrupter using two peptides as amyloid-~ models, which is a simpler strategy to evaluate the aggregation process. The first peptide (Figure IB) is an alternating arginine/phenylalanine octapeptide that forms amyloid-type ~-sheet rich fibrils and other amyloidlike analogs.2 The second one contains L-proline as the amine termination (Figure I C). In our thioflavin T (ThT) assays, peptides alone showed complete aggregation, whereas peptides coincubated with Rul exhibited significantly reduced aggregation (Figure II). Besides that, we have also developed studies regarding the disruption of mature peptide aggregates (Figure Ill). For this purpose, a Rul solution was added in an aged peptide+ ThT solution. It was verified that after a period of -10 minutes the addition of Rul led to aggregates disarrangement. We expect to provide a full description of the inhibition and disruption processes of the peptide aggregates in solution. The main goal is unveil the in-situ structure of self-assemblies and verify how the ruthenium complex acts on the structures. Our findings are expected to contribute for understanding the amyloid cascade and provide subsidies for therapeutic applications of ruthenium complexes in AD.