Interactions of an acidic cyclooctapeptide with metal ions: microcalorimetric and fluorescence analyses

Abstract

Abstract: The metal‐ion binding preferences of an acidic amphipathic cyclopeptide, cyclo[d‐Leu‐Leu‐d‐Leu‐Trp‐(d‐Glu‐Glu)2] (CP), was studied by isothermal titration calorimetry and steady‐state fluorescence spectroscopy. CP adopted a partial beta structure, and variable temperature circular dichroism showed small secondary structural changes over the temperature range from 5 °C to 95 °C. The peptide did not bind alkali or alkaline earth metal ions but exhibited selectivity for some divalent transition metal ions (with association constants KCu2+ 4.5 × 104 m−1, KZn2+ 1.6 × 105 m−1, KCd2+ 1.3 × 104 m−1, KHg2+ (1) 2.2 × 106 m−1, and KHg2+ (2) 6.5 × 103 m−1), for Pb2+ (2.0 × 105 m−1), and a trivalent Group III metal, Al3+ (1.6 × 105 m−1). The thermodynamic data show that the interaction between CP and these metal ions are spontaneous and entropically driven. A large range of binding enthalpies coupled with a smaller range of binding free energies of CP for these metal ions indicate an entropy–enthalpy compensation dependent on the ionic size of participating metal ions. The interaction of Pb2+, Hg2+, and Cu2+ with CP in aqueous solution specifically modulates the fluorescence emission properties of CP. The results of this study show that CP exhibits selectivity in metal‐ion binding, which is reflected in its fluorescence spectra. The observed trends can be useful for the design of heavy‐metal sensors based on fluorophore‐tagged acidic cyclopeptides.