Potent Cyclic Tetrapeptide for Lead Detoxification

Lead (Pb) is a ubiquitous poisonous metal, affecting the health of vast populations worldwide. Medications to treat Pb poisoning suffer from various limitations and are often toxic owing to insufficient metal selectivity. Here, we report a cyclic tetrapeptide that selectively binds Pb and eradicates...

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Bibliographic Details
Published inAngewandte Chemie Vol. 133; no. 22; pp. 12489 - 12493
Main Authors Mohammed, Tagwa A., Meier, Christoph M., Kalvoda, Tadeáš, Kalt, Martina, Rulíšek, Lubomír, Shoshan, Michal S.
Format Journal Article
LanguageEnglish
Published Weinheim Wiley Subscription Services, Inc 25.05.2021
Subjects
chelation therapy
Chemistry
Detoxification
Lead
lead poisoning
metal selectivity
Peptides
Poisoning
rational design
Selectivity
Toxicity
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Summary:Lead (Pb) is a ubiquitous poisonous metal, affecting the health of vast populations worldwide. Medications to treat Pb poisoning suffer from various limitations and are often toxic owing to insufficient metal selectivity. Here, we report a cyclic tetrapeptide that selectively binds Pb and eradicates its toxic effect on the cellular level, with superior potency than state‐of‐the‐art drugs. The Pb‐peptide complex is remarkably strong and was characterized experimentally and computationally. Accompanied by the lack of toxicity and enhanced stability of this peptide, these qualities indicate its merit as a potential remedy for Pb poisoning. Cyclic tetrapeptides were designed and screened for their ability to recover Pb‐poisoned bacteria and human cells. Excellent potency was identified with two members, outcompeting the benchmark clinical chelating agents. The leading peptide was further characterized, revealing an outstanding metal affinity and selectivity, indicating its great potential as a next‐generation treatment for Pb poisoning.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.202103217