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Amphiphilic (di-)gradient copoly(2-oxazoline)s are potent amyloid fibril formation inhibitors
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SYSNO ASEP 0574970 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Amphiphilic (di-)gradient copoly(2-oxazoline)s are potent amyloid fibril formation inhibitors Tvůrce(i) Holubová, Monika (UMCH-V) ORCID, RID
Kronek, J. (SK)
Datta, S. (SK)
Lobaz, Volodymyr (UMCH-V) RID, ORCID
Hromádková, Jiřina (UMCH-V) RID
Štěpánek, Petr (UMCH-V) RID, ORCID
Hrubý, Martin (UMCH-V) RID, ORCIDČíslo článku 113521 Zdroj.dok. Colloids and Surfaces B-Biointerfaces. - : Elsevier - ISSN 0927-7765
Roč. 230, October (2023)Poč.str. 11 s. Jazyk dok. eng - angličtina Země vyd. NL - Nizozemsko Klíč. slova amyloid fibrils ; poly(2-oxazoline) ; lysozyme Vědní obor RIV CD - Makromolekulární chemie Obor OECD Polymer science CEP GA21-01090S GA ČR - Grantová agentura ČR LM2023053 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Omezený přístup Institucionální podpora UMCH-V - RVO:61389013 UT WOS 001067547600001 EID SCOPUS 85169589245 DOI 10.1016/j.colsurfb.2023.113521 Anotace Amyloidoses are diseases caused by the accumulation of normally soluble proteins in the form of insoluble amyloids, leading to the gradual dysfunction and failure of various organs and tissues. Inhibiting amyloid formation is therefore an important therapeutic target. We hypothesized that mono- and di-gradient amphiphilic copolymers of hydrophilic 2-(m)ethyl-2-oxazoline and hydrophobic 2-aryl-2-oxazolines may inhibit amyloid fibril formation. In the model system with hen egg white lysozyme (HEWL) as amyloidogenic protein we determined the effect of these polymers on the amyloid formation by making use of the thioflavin T fluorescence, transmission electron microscopy, isothermal titration calorimetry, and dynamic light scattering. We found that some gradient copolymers possess very potent concentration-dependent inhibitory effects on HEWL amyloid formation. Structure-activity relationship revealed that copolymers with higher ratios of aromatic monomeric units had stronger amyloid suppression effects, most plausibly due to the combination of hydrophobic and π-π interactions. The measurements also revealed that the polymers that inhibit amyloid formation most plausibly do so in the form of micelles that interact with the growing amyloid fibril ends, not with isolated HEWL molecules in solution. These findings suggest the potential use of these gradient copolymers as therapeutic agents for amyloidoses. Pracoviště Ústav makromolekulární chemie Kontakt Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Rok sběru 2024 Elektronická adresa https://www.sciencedirect.com/science/article/pii/S0927776523003995?via%3Dihub
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