Počet záznamů: 1
Glucagon-like peptide 1 aggregates into low-molecular-weight oligomers off-pathway to fibrillation
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SYSNO ASEP 0572653 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Glucagon-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. 2475-2488Poč.str. 14 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova aggregation ; amyloid ; oligomers ; glucagon-like peptide 1 ; self-assembly Obor OECD Physical chemistry CEP GA22-33060S GA ČR - Grantová agentura ČR Způsob publikování Open access Institucionální podpora UOCHB-X - RVO:61388963 UT WOS 001033503000001 EID SCOPUS 85160104450 DOI 10.1016/j.bpj.2023.04.027 Anotace The 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. Pracoviště Ústav organické chemie a biochemie Kontakt asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Rok sběru 2024 Elektronická adresa https://doi.org/10.1016/j.bpj.2023.04.027
Počet záznamů: 1