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Gold complexes inhibit the aggregation of prion neuropeptides

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Abstract

Prion diseases are characterized by conformational conversion of prion protein from a normal cellular form to an abnormal scrapie isoform (PrPSc). PrP106–126 is a prion neuropeptide and an accepted model used to study the characteristics of PrPSc because such a model has biological and physiochemical properties similar to those of PrPSc. Some metal complexes have a strong binding affinity for PrP106–126 and a good inhibitory effect against amyloid fibril formation. However, the effects of the metal ligand configuration on peptide binding and aggregation are not well known. To investigate interaction and peptide aggregation between prion neuropeptides and two gold complexes with different ligand configurations ([Au(bpy)Cl2]PF6 and [Au(dien)Cl]Cl2, where bpy is 2,2′-bipyridine and dien is diethylenetriamine), six prion peptides with either a His111-mutated or a Met109/112-mutated residue were used in this study. The selection of the mutant was based on the corresponding neuropeptide from other species. The results showed that the aromatic gold complex [Au(bpy)Cl2]PF6 exhibits better binding affinity and a better inhibitory effect against peptide aggregation than the tridentate complex [Au(dien)Cl]Cl2. For the sequence–specific PrP106–126 and its mutants, His111 plays the most important role in peptide aggregation and binding affinity. Furthermore, Met112 has a greater effect on the binding affinity than Met109. Compared with the mutated short 14 amino acid peptides, the hydrophobic region of PrP106–126 contributes to both binding affinity and self-aggregation behavior. This work will help to understand and develop potential metallodrugs against amyloid disorder.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (no. 21271185), the National Basic Research Program (no. 2011CB808503), and the Fundamental Research Funds for the Central Universities and the Research Funds of Renmin University of China (no. 10XNJ011).

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  1. Department of Chemistry, Renmin University of China, Beijing, 100872, China

    Xuesong Wang, Lei He, Cong Zhao, Weihong Du & Jun Lin

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  1. Xuesong Wang
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Correspondence to Weihong Du or Jun Lin.

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Wang, X., He, L., Zhao, C. et al. Gold complexes inhibit the aggregation of prion neuropeptides. J Biol Inorg Chem 18, 767–778 (2013). https://doi.org/10.1007/s00775-013-1030-4

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