The natural tripeptide glutathione (GSH) is a ubiquitous compound harboring various biological tasks, among them interacting with essential and toxic metal ions. Yet, although weakly binding the poisonous metal lead (Pb), GSH poorly detoxifies it. β-Mercaptoaspartic acid is a new-to-nature novel amino acid that was found to enhance the Pb-detoxification capability of a synthetic cyclic tetrapeptide. Aiming to explore the advantages of noncanonical amino acids (ncAAs) of this nature, we studied the detoxification capabilities of GSH and three analogue peptides, each of which contains at least one ncAA that harbors both free carboxylate and thiolate groups. A thorough investigation that includes in vitro detoxification and mechanistic evaluations, metal-binding affinity, metal selectivity, and computational studies shows that these ncAAs are highly beneficial in additively enhancing Pb binding and reveals the importance of both high affinity and metal selectivity in synergistically reducing Pb toxicity in cells. Hence, such ncAAs join the chemical toolbox against Pb poisoning and pollution, enabling peptides to strongly and selectively bind the toxic metal ion.

• MeSH
• glutathion * chemie   metabolismus   MeSH
• kyseliny karboxylové chemie   farmakologie   MeSH
• lidé MeSH
• molekulární struktura MeSH
• olovo * chemie   MeSH
• sulfhydrylové sloučeniny * chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glutathion * MeSH
• kyseliny karboxylové MeSH
• olovo * MeSH
• sulfhydrylové sloučeniny * MeSH

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.

• Klíčová slova
• chelation therapy, lead poisoning, metal selectivity, peptides, rational design,
• MeSH
• buňky HT-29 MeSH
• cyklické peptidy chemie   metabolismus   MeSH
• lidé MeSH
• oligopeptidy chemie   metabolismus   MeSH
• olovo chemie   metabolismus   toxicita   MeSH
• vazba proteinů MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cyklické peptidy MeSH
• oligopeptidy MeSH
• olovo MeSH