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Cyclic Octapeptides Composed of Two Glutathione Units Outperform the Monomer in Lead Detoxification
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SYSNO ASEP 0557865 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Cyclic Octapeptides Composed of Two Glutathione Units Outperform the Monomer in Lead Detoxification Tvůrce(i) Sauser, L. (CH)
Kalvoda, Tadeáš (UOCHB-X) ORCID
Kavas, A. (CH)
Rulíšek, Lubomír (UOCHB-X) RID, ORCID
Shoshan, M. S. (CH)Číslo článku e202200152 Zdroj.dok. ChemMedChem. - : Wiley - ISSN 1860-7179
Roč. 17, č. 15 (2022)Poč.str. 7 s. Jazyk dok. eng - angličtina Země vyd. DE - Německo Klíč. slova lead ; peptides ; chelates ; glutathione ; bioinoganic chemistry Obor OECD Physical chemistry CEP GA20-08772S GA ČR - Grantová agentura ČR Způsob publikování Open access Institucionální podpora UOCHB-X - RVO:61388963 UT WOS 000799312900001 EID SCOPUS 85130498319 DOI 10.1002/cmdc.202200152 Anotace A rationally-designed scaffold of cyclic octapeptides composed of two units of the natural tripeptide glutathione (GSH) was optimized to strongly and selectively capture toxic lead ions (Pb(II)). Using state-of-the-art computational tools, a list of eleven plausible peptides was shortened to five analogs based on their calculated affinity to Pb(II) ions. We then synthesized and investigated them for their abilities to recover Pb-poisoned human cells. A clear pattern was observed from the in vitro detoxification results, indicating the importance of cavity size and polar moieties to enhance metal capturing. These, together with the apparent benefit of cyclizing the peptides, improved the detoxification of the two lead peptides by approximately two folds compared to GSH and the benchmark chelating agents against Pb poisoning. Moreover, the two peptides did not show any toxicity and, therefore, were thoroughly investigated to determine their potential as next-generation remedies for Pb poisoning. Pracoviště Ústav organické chemie a biochemie Kontakt asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Rok sběru 2023 Elektronická adresa https://doi.org/10.1002/cmdc.202200152
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