title: Designing peptidic inhibitors of serum amyloid A aggregation process.
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.
authors.affiliation: Department of Biomedical Chemistry, Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308, Gdańsk, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Sosnowska
authors.affiliation: Department of Biomedical Chemistry, Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308, Gdańsk, Poland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Skibiszewska
authors.affiliation: Department of Biomedical Chemistry, Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308, Gdańsk, Poland.
authors.forename: Emilia
authors.initials: E
authors.lastname: Kamińska
authors.affiliation: Department of Biomedical Chemistry, Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308, Gdańsk, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Wieczerzak
authors.affiliation: Department of Biomedical Chemistry, Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308, Gdańsk, Poland. elzbieta.jankowska@ug.edu.pl.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Jankowska
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological / Q000517:prevention & control*; D000685:Serum Amyloid A Protein / Q000037:antagonists & inhibitors*; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D016229:Amyloid beta-Peptides; D066329:Protein Aggregates; D000685:Serum Amyloid A Protein; D012996:Solutions
keywords: Fibrillization; Fluorescence; Fourier transform infrared spectroscopy (FTIR); Inhibitor; Serum amyloid A; Transmission electron microscopy (TEM)