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Dithiolated Peptides with Tryptophan Residues as Potential Chelators for Mercury (II)

T'ea Cameron, Charlexia Witcher, Dr. Maria Ngu-Schwemlein, Department of Chemistry, Winston-Salem State University, 601 S Martin Luther King Jr Dr, Winston-Salem NC 27110

Mercury poisoning is a prevalent problem that adversely affect the nervous, digestive,
and immune system. Current clinical drugs used in mercury chelation therapy depends on the
complexation of mercury(II) ions with these dithiol compounds. However, they are not optimal
chelators and show some side effects; therefore, there is a need for new drugs to treat mercury
toxicity. We are currently evaluating dicysteinyl peptides as chelating agents for mercury(II). In
this research study we designed dithiolated peptides containing one or two tryptophan (Trp)
residues as auxiliary binding groups for mercury(II). We postulate that the cysteinyl thiol groups
could coordinate mercury(II) and form linear complexes consisting of Hg(II)---S bonds; and that
the indole side chain of tryptophan could enhance mercury binding via pi-cation interactions. We
designed dicysteinyl peptides with a Cys-Trp-Cys motif, and then incorporate a second Trp
residue at the N- or C-terminal. The complexation of pentapeptides Gly-Cys-Trp-Cys-Gly (P1),
Trp-Cys-Trp-Cys-Gly (P2), and Gly-Cys-Trp-Cys-Trp (P3) with mercury(II) to form Hg---S bonds
were studied by UV spectrophotometry. The secondary structure of the peptide and pi-cation
interactions were evaluated by circular dichroism (CD) spectroscopy. The UV spectroscopic
results show ligand-metal-charge-transfer and absorption at ca. 220 nm that is characteristic of
Hg(II)---S bond formation. CD spectra show that these peptides undergo secondary structural
changes on binding Hg(II), and the presence of pi-cation interactions. Significant fluorescence
quenching of the indole side chain group of Trp confirmed their proximity to Hg(II). These
findings will be useful for the rational design of more effective mercury chelators to improve
efficacy in treating mercury poisoning.

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