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Cyclic Octapeptides Composed of Two Glutathione Units Outperform the Monomer in Lead Detoxification

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 an...

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Autores principales: Sauser, Luca, Kalvoda, Tadeáš, Kavas, Ayça, Rulíšek, Lubomír, Shoshan, Michal S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9544108/
https://www.ncbi.nlm.nih.gov/pubmed/35560783
http://dx.doi.org/10.1002/cmdc.202200152
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author Sauser, Luca
Kalvoda, Tadeáš
Kavas, Ayça
Rulíšek, Lubomír
Shoshan, Michal S.
author_facet Sauser, Luca
Kalvoda, Tadeáš
Kavas, Ayça
Rulíšek, Lubomír
Shoshan, Michal S.
author_sort Sauser, Luca
collection PubMed
description 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.
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spelling pubmed-95441082022-10-14 Cyclic Octapeptides Composed of Two Glutathione Units Outperform the Monomer in Lead Detoxification Sauser, Luca Kalvoda, Tadeáš Kavas, Ayça Rulíšek, Lubomír Shoshan, Michal S. ChemMedChem Research Articles 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. John Wiley and Sons Inc. 2022-05-24 2022-08-03 /pmc/articles/PMC9544108/ /pubmed/35560783 http://dx.doi.org/10.1002/cmdc.202200152 Text en © 2022 The Authors. ChemMedChem published by Wiley-VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Sauser, Luca
Kalvoda, Tadeáš
Kavas, Ayça
Rulíšek, Lubomír
Shoshan, Michal S.
Cyclic Octapeptides Composed of Two Glutathione Units Outperform the Monomer in Lead Detoxification
title Cyclic Octapeptides Composed of Two Glutathione Units Outperform the Monomer in Lead Detoxification
title_full Cyclic Octapeptides Composed of Two Glutathione Units Outperform the Monomer in Lead Detoxification
title_fullStr Cyclic Octapeptides Composed of Two Glutathione Units Outperform the Monomer in Lead Detoxification
title_full_unstemmed Cyclic Octapeptides Composed of Two Glutathione Units Outperform the Monomer in Lead Detoxification
title_short Cyclic Octapeptides Composed of Two Glutathione Units Outperform the Monomer in Lead Detoxification
title_sort cyclic octapeptides composed of two glutathione units outperform the monomer in lead detoxification
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9544108/
https://www.ncbi.nlm.nih.gov/pubmed/35560783
http://dx.doi.org/10.1002/cmdc.202200152
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