Amphiphilic (di-)gradient copoly(2-oxazoline)s are potent amyloid fibril formation inhibitors

0574970 - ÚMCH 2024 RIV NL eng J - Journal Article
Holubová, Monika - Kronek, J. - Datta, S. - Lobaz, Volodymyr - Hromádková, Jiřina - Štěpánek, Petr - Hrubý, Martin
Amphiphilic (di-)gradient copoly(2-oxazoline)s are potent amyloid fibril formation inhibitors.
Colloids and Surfaces B-Biointerfaces. Roč. 230, October (2023), č. článku 113521. ISSN 0927-7765. E-ISSN 1873-4367
R&D Projects: GA ČR(CZ) GA21-01090S; GA MŠMT(CZ) LM2023053
Institutional support: RVO:61389013
Keywords : amyloid fibrils * poly(2-oxazoline) * lysozyme
OECD category: Polymer science
Impact factor: 5.8, year: 2022
Method of publishing: Limited access
https://www.sciencedirect.com/science/article/pii/S0927776523003995?via%3Dihub

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.
Permanent Link: https://hdl.handle.net/11104/0345371