α-Synuclein Dimers as Potent Inhibitors of Fibrillization

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F19%3A00511507" target="_blank" >RIV/61388963:_____/19:00511507 - isvavai.cz</a>

Výsledek na webu

<a href="https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.9b01400" target="_blank" >https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.9b01400</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jmedchem.9b01400" target="_blank" >10.1021/acs.jmedchem.9b01400</a>

Jazyk výsledku

angličtina

Název v původním jazyce

α-Synuclein Dimers as Potent Inhibitors of Fibrillization

Popis výsledku v původním jazyce

Aggregation of the neuronal protein α-synuclein into amyloid fibrils plays a central role in the development of Parkinson’s disease. Growth of fibrils can be suppressed by blocking fibril ends from their interaction with monomeric proteins. In this work, we constructed inhibitors that bind to the ends of α-synuclein amyloid fibrils with very high affinity. They are based on synthetic α-synuclein dimers and interact with fibrils via two monomeric subunits adopting conformation that efficiently blocks fibril elongation. By tuning the charge of dimers, we further enhanced the binding affinity and prepared a construct that inhibits fibril elongation at nanomolar concentration (IC50 ≈ 20 nM). To the best of our knowledge, it is the most efficient inhibitor of α-synuclein fibrillization.

Název v anglickém jazyce

α-Synuclein Dimers as Potent Inhibitors of Fibrillization

Popis výsledku anglicky

Aggregation of the neuronal protein α-synuclein into amyloid fibrils plays a central role in the development of Parkinson’s disease. Growth of fibrils can be suppressed by blocking fibril ends from their interaction with monomeric proteins. In this work, we constructed inhibitors that bind to the ends of α-synuclein amyloid fibrils with very high affinity. They are based on synthetic α-synuclein dimers and interact with fibrils via two monomeric subunits adopting conformation that efficiently blocks fibril elongation. By tuning the charge of dimers, we further enhanced the binding affinity and prepared a construct that inhibits fibril elongation at nanomolar concentration (IC50 ≈ 20 nM). To the best of our knowledge, it is the most efficient inhibitor of α-synuclein fibrillization.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GJ18-06255Y" target="_blank" >GJ18-06255Y: Nová strategie pro inhibici tvorby amyloidních fibril</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Journal of Medicinal Chemistry

ISSN

0022-2623

e-ISSN

—

Svazek periodika

62

Číslo periodika v rámci svazku

22

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

10342-10351

Kód UT WoS článku

000500420100021

EID výsledku v databázi Scopus

2-s2.0-85074723394