De Novo Design and Spectroscopic Characterization of a Dinucleating Copper-Binding Pentadecapeptide

A spectroscopic study of aqueous solutions of Ac−WGHGHGHGPGHGHGH−NH<sub>2</sub> (HGP) indicates that copper(II) binds to the peptide to form a 2:1 Cu<sup>2+</sup>/HGP complex with four nitrogen atoms in the copper coordination environment. Electron paramagnetic resonance (EPR) and UV−visible data suggest copper binding through the peptide backbone and imidazole nitrogen donors. Circular dichroism data show that HGP is unbound below pH 5.5 and is copper-saturated at pH 9 and above. The apo form of the peptide is unstructured in solution and is organized into a turn conformation in the presence of 2 mol equiv of Cu<sup>2+</sup> at basic pH. EPR measurements for 2:1 Cu<sup>2+</sup>/HGP solutions in the <i>g</i> = 2 region and within the pH range 7−11 exhibit axial spectra. A molecular-mechanics-minimized model of the Cu<sup>2+</sup>/HGP complex gave a Cu···Cu separation of 8 Å.