Copper(ii) complexes of terminally free alloferon mutants containing two histidyl binding sites inside peptide chain structure and stability?

Dalton Transactions Pub Date: 2015-10-28 DOI: 10.1039/C5DT01911G

Abstract

Mononuclear and polynuclear copper(II) complexes of alloferon 1 with point mutations, H1A/H12A H2N-A1GVSGH6GQH9GVA12G-COOH, H1A/H9A H2N-A1GVSGH6GQA9GVH12G-COOH, and H1A/H6A H2N-A1GVSGA6GQH9GVH12G-COOH, have been studied by potentiometric, UV-visible, CD, and EPR spectroscopy, and mass spectrometry (MS) methods. Complete complex speciation at different metal-to-ligand molar ratios ranging from 1?:?1 to 3?:?1 was obtained. Over a wide 6–8 pH range, including physiological pH 7.4, and a 1?:?1 metal-to-ligand molar ratio, the peptides studied formed a CuH?1L complex with the 4N{NH2,N?,2NIm} coordination mode. The presence of the 4N binding site for the CuH?1L complexes prevented the deprotonation and coordination of the second amide nitrogen atom to copper(II) ions (pK?1/?2 7.83–8.07) compared to that of pentaGly (6.81). The amine nitrogen donor and two imidazole nitrogen atoms (H6H9, H6H12 and H9H12) can be considered to be independent metal-binding sites in the species formed. As a consequence, di- and trinuclear complexes for the metal-to-ligand 2?:?1 and 3?:?1 molar ratios dominate in the solution, respectively. For the Cu(II)-H1A/H9A and Cu(II)-H1A/H12A systems, the Cu3H?9L complexes are likely formed by the coordination of amide nitrogen atoms towards C-termini with ring sizes (7,5,5).

Graphical abstract: Copper(ii) complexes of terminally free alloferon mutants containing two histidyl binding sites inside peptide chain structure and stability
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