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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F22%3A00557865" target="_blank" >RIV/61388963:_____/22:00557865 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1002/cmdc.202200152" target="_blank" >https://doi.org/10.1002/cmdc.202200152</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/cmdc.202200152" target="_blank" >10.1002/cmdc.202200152</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

<a href="/cs/project/GA20-08772S" target="_blank" >GA20-08772S: Objevování základních principů struktury proteinů a protein-ligandových komplexů pokročilými metodami kvantové chemie</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

ChemMedChem

ISSN

1860-7179

e-ISSN

1860-7187

Svazek periodika

17

Číslo periodika v rámci svazku

15

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

7

Strana od-do

e202200152

Kód UT WoS článku

000799312900001

EID výsledku v databázi Scopus

2-s2.0-85130498319