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Designing peptidic inhibitors of serum amyloid A aggregation process

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Abstract

Amyloid A amyloidosis is a life-threatening complication of a wide range of chronic inflammatory, infectious and neoplastic diseases, and the most common form of systemic amyloidosis worldwide. It is characterized by extracellular tissue deposition of fibrils that are composed of fragments of serum amyloid A protein (SAA), a major acute-phase reactant protein, produced predominantly by hepatocytes. Currently, there are no approved therapeutic agents directed against the formation of fibrillar SAA assemblies. We attempted to develop peptidic inhibitors based on their similarity and complementarity to the regions critical for SAA self-association, which they should interact with and block their assembly into amyloid fibrils. Inh1 and inh4 which are comprised of the residues from the amyloidogenic region of SAA1.1 protein and Aβ peptide, respectively, were found by us as capable to significantly suppress aggregation of the SAA1-12 peptide. It was chosen as an aggregation model that mimicks the amyloidogenic nucleus of SAA protein. We suppose that aromatic interactions may be responsible for inhibitory activity of both compounds. We also recognized that aromatic residues are involved in self-association of SAA1-12.

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Acknowledgments

This work was financially supported by grants of the National Science Center 2011/03/N/NZ5/01460 and the University of Gdansk DS 530-8725-D496-15.

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Authors and Affiliations

  1. Department of Biomedical Chemistry, Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308, Gdańsk, Poland

    Marta Sosnowska, Sandra Skibiszewska, Emilia Kamińska, Ewa Wieczerzak & Elżbieta Jankowska

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  1. Marta Sosnowska
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  2. Sandra Skibiszewska
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  3. Emilia Kamińska
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  4. Ewa Wieczerzak
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  5. Elżbieta Jankowska
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Correspondence to Elżbieta Jankowska.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Handling Editor: J. D. Wade.

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Sosnowska, M., Skibiszewska, S., Kamińska, E. et al. Designing peptidic inhibitors of serum amyloid A aggregation process. Amino Acids 48, 1069–1078 (2016). https://doi.org/10.1007/s00726-015-2167-y

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  • DOI: https://doi.org/10.1007/s00726-015-2167-y

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