Thiolation and Carboxylation of Glutathione Synergistically Enhance Its Lead-Detoxification Capabilities

0550071 - ÚOCHB 2022 RIV US eng J - Článek v odborném periodiku
Sauser, L. - Mohammed, T. A. - Kalvoda, Tadeáš - Feng, S.-J. - Spingler, B. - Rulíšek, Lubomír - Shoshan, M. S.
Thiolation and Carboxylation of Glutathione Synergistically Enhance Its Lead-Detoxification Capabilities.
Inorganic Chemistry. Roč. 60, č. 24 (2021), s. 18620-18624. ISSN 0020-1669. E-ISSN 1520-510X
Institucionální podpora: RVO:61388963
Klíčová slova: amino acids * binding energy * carboxylation
Obor OECD: Physical chemistry
Impakt faktor: 5.436, rok: 2021
Způsob publikování: Omezený přístup
https://doi.org/10.1021/acs.inorgchem.1c03030

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.
Trvalý link: http://hdl.handle.net/11104/0325923