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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F23%3A00574970" target="_blank" >RIV/61389013:_____/23:00574970 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/23:10480087

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0927776523003995?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0927776523003995?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.colsurfb.2023.113521" target="_blank" >10.1016/j.colsurfb.2023.113521</a>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10404 - Polymer science

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Colloids and Surfaces B-Biointerfaces

ISSN

0927-7765

e-ISSN

1873-4367

Volume of the periodical

230

Issue of the periodical within the volume

October

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

11

Pages from-to

113521

UT code for WoS article

001067547600001

EID of the result in the Scopus database

2-s2.0-85169589245