Rationally Designed Protein-Based Inhibitor of α-Synuclein Fibrillization in Cells
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F21%3A00543021" target="_blank" >RIV/61388963:_____/21:00543021 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11310/21:10430068
Result on the web
<a href="https://doi.org/10.1021/acs.jmedchem.1c00086" target="_blank" >https://doi.org/10.1021/acs.jmedchem.1c00086</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jmedchem.1c00086" target="_blank" >10.1021/acs.jmedchem.1c00086</a>
Alternative languages
Result language
angličtina
Original language name
Rationally Designed Protein-Based Inhibitor of α-Synuclein Fibrillization in Cells
Original language description
Misfolding of the neuronal protein α-synuclein (αSyn) into amyloid fibrils is involved in the development of Parkinson’s disease (PD), and inhibition of this process is considered to be a promising therapeutic approach. In this work, we engineered protein inhibitors that bind to fibrils with higher affinity than the monomeric αSyn. They were developed based on the recent structural data of the αSyn fibrils and were shown to prevent fibril elongation upon binding to fibril ends. These inhibitors are highly selective to the misfolded αSyn, nontoxic, and active in cytosol in small concentrations. The best-performing inhibitor shows IC50 ∼10 nM in a cell-based assay, which corresponds to the ∼1:60 molar ratio to αSyn. It can suppress the formation of αSyn aggregates in cells that can be potentially used to slow down the spreading of the pathological aggregates from cell to cell during the course of the PD.
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
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/GJ18-06255Y" target="_blank" >GJ18-06255Y: New strategy for inhibition of amyloid fibril formation</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
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
1520-4804
Volume of the periodical
64
Issue of the periodical within the volume
10
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
6827-6837
UT code for WoS article
000657351500023
EID of the result in the Scopus database
2-s2.0-85106523673