Potent Cyclic Tetrapeptide for Lead Detoxification. Issue 22 (28th April 2021)

• Record Type: Journal Article
• Authors: Mohammed, Tagwa A.; Meier, Christoph M.; Kalvoda, Tadeáš; Kalt, Martina; Rulíšek, Lubomír; Shoshan, Michal S.
• Is Part Of: Angewandte Chemie international edition. Volume 60:Issue 22(2021)
• Page Start: 12381
• Page End: 12385
• Publication Date: 2021-04-28
• Subjects: chelation therapy -- lead poisoning -- metal selectivity -- peptides -- rational design; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202103217
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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. Abstract : 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.