alpha-Synuclein Dimers as Potent Inhibitors of Fibrillization
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F19%3A10403953" target="_blank" >RIV/00216208:11310/19:10403953 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=SiLQPndl8o" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=SiLQPndl8o</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jmedchem.9b01400" target="_blank" >10.1021/acs.jmedchem.9b01400</a>
Alternative languages
Result language
angličtina
Original language name
alpha-Synuclein Dimers as Potent Inhibitors of Fibrillization
Original language description
Aggregation of the neuronal protein alpha-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 alpha-synuclein amyloid fibrils with very high affinity. They are based on synthetic alpha-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 approximate to 20 nM). To the best of our knowledge, it is the most efficient inhibitor of alpha-synuclein fibrillization.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
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Continuities
S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Medicinal Chemistry
ISSN
0022-2623
e-ISSN
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Volume of the periodical
62
Issue of the periodical within the volume
22
Country of publishing house
US - UNITED STATES
Number of pages
10
Pages from-to
10342-10351
UT code for WoS article
000500420100021
EID of the result in the Scopus database
2-s2.0-85074723394