Disclosing the Preferential Mercury Chelation by SeCys Containing Peptides over Their Cys Analogues

Area of Science:

• Biochemistry
• Toxicology
• Medicinal Chemistry

Background:

• Vasopressin, a cyclic nonapeptide hormone, contains cysteine residues crucial for its structure and function.
• Mercury compounds, particularly methylmercury, pose significant environmental and health risks due to their toxicity.
• Understanding the interaction between mercury species and biologically relevant peptides is vital for developing detoxification strategies.

Purpose of the Study:

• To investigate the reaction of mercury (I), mercury (II), and methylmercury chlorides with vasopressin and its selenium-containing analogues.
• To evaluate the impact of cysteine-to-selenocysteine substitution on peptide reactivity towards methylmercury.
• To explore the potential of selenopeptides as chelating agents for methylmercury detoxification.

Main Methods:

• Synthesis of vasopressin mono- and diselenium analogues.
• Incubation of peptides with various mercury chloride species (Hg(I), Hg(II), CH3HgCl).
• Analysis of mercury-peptide adducts using techniques to determine binding sites and structures.
• Competitive binding experiments to assess preferential mercury chelation.

Main Results:

• Vasopressin and its selenium analogues form adducts with mercury compounds.
• Replacement of cysteine with selenocysteine in vasopressin enhances reactivity towards methylmercury.
• Predominant formation of -Se/S-Hg-Se-bridged structures, leading to methylmercury demethylation.
• Diselenium vasopressin analogue preferentially binds methylmercury and can displace mercury from sulfur-bound sites.

Conclusions:

• Selenopeptides exhibit increased reactivity and affinity for methylmercury compared to native vasopressin.
• The formation of selenide-bridged mercury adducts is a key mechanism in methylmercury detoxification.
• Selenopeptides represent a promising therapeutic approach for methylmercury chelation and mitigating its toxic effects.