Amphiphilic (di-)gradient copoly(2-oxazoline)s are potent amyloid fibril formation inhibitors
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články
PubMed
37634283
DOI
10.1016/j.colsurfb.2023.113521
PII: S0927-7765(23)00399-5
Knihovny.cz E-zdroje
- Klíčová slova
- Amyloid fibrils, Amyloidosis, Gradient copolymers, Lysozyme, Poly(2-oxazoline),
- MeSH
- amyloid * MeSH
- amyloidogenní proteiny MeSH
- amyloidóza * MeSH
- kalorimetrie MeSH
- lidé MeSH
- polymery MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- amyloid * MeSH
- amyloidogenní proteiny MeSH
- polymery MeSH
MOTIVATION: 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. HYPOTHESIS: 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. EXPERIMENTS: 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. FINDINGS: 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.
Citace poskytuje Crossref.org
