Influence of short peptides with aromatic amino acid residues on aggregation properties of serum amyloid A and its fragments

Sandra Skibiszewska , Szymon Żaczek , Agnieszka Dybala-Defratyka , Katarzyna Jędrzejewska , Elżbieta Jankowska

Abstract

Serum amyloid A variant 1.1 (SAA1.1) is an acute phase protein. In response to injury, inflammation or infection its production increases highly, which may lead to aggregation of the protein and accumulation of its deposits in various organs. Due to the cellular toxicity of the aggregates, as well as the fact that accumulated deposits are a burden that obstructs proper functioning of the affected tissues, it is vital to find a way to suppress the process of pathological aggregates formation. To make this possible, it is necessary to investigate thoroughly the oligomerization process and recognize factors that may influence its course. Some previous studies showed that aromatic interactions are important to the potential of an inhibitor to suppress the aggregation process. In our research we had proved that a five-residue peptide RSFFS (saa1-5) is an efficient inhibitor of aggregation of the most amyloidogenic fragment of SAA1.1, SAA1-12. In the present work the oligomerization and aggregation propensity of SAA1-12 was compared to that of SAA1-27, in order to determine the contribution of the sequence which extends beyond the most amyloidogenic region but encompasses residues reportedly involved in the stabilization of the SAA native conformation. Thioflavin T fluorescence assay, quantitative chromatographic analysis of the insoluble fraction and transmission electron microscopy allowed for a deeper insight into the SAA aggregation process and the morphology of aggregates. Substitutions of Phe3 and/or Phe4 residues in saa1-5 sequence with tryptophan, tyrosine, homophenylalanine, naphthylalanine and β,β-diphenylalanine allowed to study the influence of different aromatic systems on the aggregation of SAA1-12 and SAA1-27, and evaluate these results in relation to hSAA1.1 protein. Our results indicate that compounds with aromatic moieties can affect the course of the aggregation process and change the ratio between the soluble and insoluble aggregates.
Author Sandra Skibiszewska (FCh / DBCh / LMCh)
Sandra Skibiszewska,,
- Laboratory of Medical Chemistry
, Szymon Żaczek
Szymon Żaczek,,
-
, Agnieszka Dybala-Defratyka
Agnieszka Dybala-Defratyka,,
-
, Katarzyna Jędrzejewska (FCh / DBCh / LMCh)
Katarzyna Jędrzejewska,,
- Laboratory of Medical Chemistry
, Elżbieta Jankowska (FCh / DBCh / LMCh)
Elżbieta Jankowska,,
- Laboratory of Medical Chemistry
Journal seriesArchives of Biochemistry and Biophysics, ISSN 0003-9861, e-ISSN 1096-0384, (N/A 100 pkt)
Issue year2020
Vol681
Pages1-8
Publication size in sheets0.5
Article number108264
Keywords in EnglishSerum amyloid A, amyloidosis, aggregate, soluble oligomer, aromatic interaction
ASJC Classification1303 Biochemistry; 1304 Biophysics; 1312 Molecular Biology
DOIDOI:10.1016/j.abb.2020.108264
Languageen angielski
LicenseRepository; published final; Uznanie Autorstwa - Użycie Niekomercyjne - Bez utworów zależnych (CC-BY-NC-ND); with publication
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Skibiszewska_Sandra_Influence_of_short_peptides_2020.pdf 2.08 MB
Score (nominal)100
Score sourcejournalList
ScoreMinisterial score = 100.0, 08-02-2020, ArticleFromJournal
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2018 = 0.998; WoS Impact Factor: 2018 = 3.559 (2) - 2018=3.269 (5)
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LicencjaUtwór jest udostępniany na licencji Creative Commons Uznanie autorstwa-Użycie niekomercyjne-Bez utworów zależnych 4.0 Międzynarodowe (CC BY-NC-ND 4.0) https://creativecommons.org/licenses/by-nc-nd/4.0/
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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