Thermodynamics and fluorescence studies of the interactions of cyclooctapeptides with Hg2+, Pb2+, and Cd2+

The purpose of this work is to characterize the interactions of cyclooctapeptides (CP) containing glutamyl and/or cysteinyl residues with common heavy-metal ions in order to facilitate the design of cyclopeptides as sensors for metal ions. Isothermal titration calorimetry studies show that cyclooctapeptides containing glutamyl and/or cysteinyl residues bind these Hg2+ and Pb2+ over Cd2+ and other common metal ions. Differential binding isotherms, in their interactions with Hg2+, support a two-binding site model, whereas pertinent interactions with Pb2+ support a 2:1 stoichiometry, suggesting a CP/Pb2+/CP mode of complexation. The cyclooctapeptide containing both glutamyl and cysteinyl residues shows a significant binding affinity for Hg2+ (Ka = 7.6 × 107 M−1), which is both enthalpically and entropically driven. The fluorescence of these cyclooctapeptides showed pronounced fluorescence quenching responses to Hg2+ over Pd2+ and Cd2+. Stern–Volmer analyses of the dependence of fluorescence intensity on Hg2+ and Pb2+ are reported. The observed trends are useful for the design of Hg2+ sensors based on fluorophore-tagged cyclooctapeptides.

Isothermal titration calorimetry shows that CP1-3 bind Hg2+ and Pb2+ over Cd2+. CP1-3 showed pronounced fluorescence quenching responses to Hg2+. Fluorophore-tagged cyclooctapeptides may be useful as Hg2+ sensors.Figure optionsDownload as PowerPoint slide