Počet záznamů: 1  

Glucagon-like peptide 1 aggregates into low-molecular-weight oligomers off-pathway to fibrillation

  1. 1.
    SYSNO ASEP0572653
    Druh ASEPJ - Článek v odborném periodiku
    Zařazení RIVJ - Článek v odborném periodiku
    Poddruh JČlánek ve WOS
    NázevGlucagon-like peptide 1 aggregates into low-molecular-weight oligomers off-pathway to fibrillation
    Tvůrce(i) Přáda Brichtová, E. (GB)
    Krupová, Monika (UOCHB-X) ORCID, RID
    Bouř, Petr (UOCHB-X) RID, ORCID
    Lindo, V. (GB)
    Gomes dos Santos, A. (GB)
    Jackson, S. E. (GB)
    Zdroj.dok.Biophysical Journal. - : Cell Press - ISSN 0006-3495
    Roč. 122, č. 12 (2023), s. 2475-2488
    Poč.str.14 s.
    Jazyk dok.eng - angličtina
    Země vyd.US - Spojené státy americké
    Klíč. slovaaggregation ; amyloid ; oligomers ; glucagon-like peptide 1 ; self-assembly
    Obor OECDPhysical chemistry
    CEPGA22-33060S GA ČR - Grantová agentura ČR
    Způsob publikováníOpen access
    Institucionální podporaUOCHB-X - RVO:61388963
    UT WOS001033503000001
    EID SCOPUS85160104450
    DOI10.1016/j.bpj.2023.04.027
    AnotaceThe physical stability of peptide-based drugs is of great interest to the pharmaceutical industry. Glucagon-like peptide 1 (GLP-1) is a 31-amino acid peptide hormone, the analogs of which are frequently used in the treatment of type 2 diabetes. We investigated the physical stability of GLP-1 and its C-terminal amide derivative, GLP-1-Am, both of which aggregate into amyloid fibrils. While off-pathway oligomers have been proposed to explain the unusual aggregation kinetics observed previously for GLP-1 under specific conditions, these oligomers have not been studied in any detail. Such states are important as they may represent potential sources of cytotoxicity and immunogenicity. Here, we identified and isolated stable, low-molecular-weight oligomers of GLP-1 and GLP-1-Am, using size-exclusion chromatography. Under the conditions studied, isolated oligomers were shown to be resistant to fibrillation or dissociation. These oligomers contain between two and five polypeptide chains and they have a highly disordered structure as indicated by a variety of spectroscopic techniques. They are highly stable with respect to time, temperature, or agitation despite their noncovalent character, which was established using liquid chromatography-mass spectrometry and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These results provide evidence of stable, low-molecular-weight oligomers that are formed by an off-pathway mechanism which competes with amyloid fibril formation.
    PracovištěÚstav organické chemie a biochemie
    Kontaktasep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418
    Rok sběru2024
    Elektronická adresahttps://doi.org/10.1016/j.bpj.2023.04.027
Počet záznamů: 1  

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