Počet záznamů: 1
Thermodynamic and structural characterization of an optimized peptide-based inhibitor of the influenza polymerase PA-PB1 subunit interaction
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SYSNO ASEP 0563164 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Thermodynamic and structural characterization of an optimized peptide-based inhibitor of the influenza polymerase PA-PB1 subunit interaction Tvůrce(i) Radilová, Kateřina (UOCHB-X) ORCID
Zima, Václav (UOCHB-X) RID, ORCID
Král, Michal (UOCHB-X) ORCID
Machara, Aleš (UOCHB-X) ORCID
Majer, Pavel (UOCHB-X)
Hodek, Jan (UOCHB-X) RID, ORCID
Weber, Jan (UOCHB-X) RID, ORCID
Brynda, Jiří (UOCHB-X) RID, ORCID
Strmeň, Timotej (UOCHB-X) RID, ORCID
Konvalinka, Jan (UOCHB-X) RID, ORCID
Kožíšek, Milan (UOCHB-X) RID, ORCIDČíslo článku 105449 Zdroj.dok. Antiviral Research. - : Elsevier - ISSN 0166-3542
Roč. 208, December (2022)Poč.str. 9 s. Jazyk dok. eng - angličtina Země vyd. NL - Nizozemsko Klíč. slova antiviral peptides ; influenza A polymerase ; protein-protein interaction ; AlphaScreen ; isothermal titration calorimetry Obor OECD Biochemistry and molecular biology CEP EF16_019/0000729 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy LX22NPO5103 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora UOCHB-X - RVO:61388963 UT WOS 000879832300001 EID SCOPUS 85140307737 DOI 10.1016/j.antiviral.2022.105449 Anotace Influenza virus causes severe respiratory infection in humans. Current antivirotics target three key proteins in the viral life cycle: neuraminidase, the M2 channel and the endonuclease domain of RNA-dependent-RNA polymerase. Due to the development of novel pandemic strains, additional antiviral drugs targetting different viral proteins are still needed. The protein-protein interaction between polymerase subunits PA and PB1 is one such possible target. We recently identified a modified decapeptide derived from the N-terminus of the PB1 subunit with high affinity for the C-terminal part of the PA subunit. Here, we optimized its amino acid hotspots to maintain the inhibitory potency and greatly increase peptide solubility. This allowed thermodynamic characterization of peptide binding to PA. Solving the X-ray structure of the peptide-PA complex provided structural insights into the interaction. Additionally, we optimized intracellular delivery of the peptide using a bicyclic strategy that led to improved inhibition in cell-based assays. 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 2023 Elektronická adresa https://doi.org/10.1016/j.antiviral.2022.105449
Počet záznamů: 1