Počet záznamů: 1
Rationally Designed Protein-Based Inhibitor of α-Synuclein Fibrillization in Cells
- 1.
SYSNO ASEP 0543021 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Rationally Designed Protein-Based Inhibitor of α-Synuclein Fibrillization in Cells Tvůrce(i) Priss, Anastasiia (UOCHB-X) ORCID
Afitska, Kseniia (UOCHB-X) ORCID, RID
Galkin, Maksym (UOCHB-X) ORCID
Yushchenko, Dmytro A. (UOCHB-X) ORCID, RID
Shvadchak, Volodymyr V. (UOCHB-X) ORCID, RIDZdroj.dok. Journal of Medicinal Chemistry. - : American Chemical Society - ISSN 0022-2623
Roč. 64, č. 10 (2021), s. 6827-6837Poč.str. 11 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova parkinsons disease ; aggregation ; brain Obor OECD Biochemistry and molecular biology CEP GJ18-06255Y GA ČR - Grantová agentura ČR Způsob publikování Omezený přístup Institucionální podpora UOCHB-X - RVO:61388963 UT WOS 000657351500023 EID SCOPUS 85106523673 DOI 10.1021/acs.jmedchem.1c00086 Anotace 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. Pracoviště Ústav organické chemie a biochemie Kontakt asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434 Rok sběru 2022 Elektronická adresa https://doi.org/10.1021/acs.jmedchem.1c00086
Počet záznamů: 1