Evaluating the involvement of tryptophan on thiolated peptide-mercury(II) complexes: Cation-pi interactions

Abstract

An understanding of how mercury(II) forms complexes with bis-cysteinyl peptides containing auxiliary binding groups could provide vital insights for optimal mercury immobilization. In this study, we investigate how tryptophan might participate in peptide-mercury(II) complex formation. Model pentapeptides consisting of a Cys-Xaa-Cys (CXC) sequence, where Xaa is Gly (Penta 1), Trp (Penta 2), and d-Trp (Penta 3) were designed. Their complexation with mercury(II) was studied by spectroscopic methods and molecular modeling. UV absorption difference spectra reflect the formation of bisthiolate-mercury(II) bonds. These spectra also show changes in the Bb absorption band of the indole group following complex formation. Circular Dichroism (CD) spectra indicate that mercury(II) bound peptides adopt a secondary structure resembling a type I β turn structure. Mercury(II) bound Penta 2 also develops a negative CD band at 221 nm, which suggests an association between the tryptophan indole ring and mercury(II) via cation-pi interaction. Fluorescence quenching in the presence of equimolar mercury(II) is significantly greater for Penta 2 than Penta 3. These CD and fluorescence data indicate that the indole ring of Penta 3 is not interacting with the coordinated mercury(II). Optimized 1:1 mercury(II)-peptide structures show that the indole pi system of Penta 2 participates in mercury(II) cation-pi interaction, whereas in Penta 3 it is involved in ammonium cation-pi association. These structural insights will be useful for designing more effective mercury chelators containing tryptophan as an auxiliary binding and hydrophobic shielding group in immobilizing mercury(II).