Enzyme mimics complexing Cu(II) ion: structure-function relationships

Five peptides containing (His-X-2)-His or (His-X-3)-His motifs have been de signed and synthesized to coordinate Cu(II). Structural information was obt ained by various spectroscopic techniques and was used as constraint to sea rch for local conformational energy minima by molecular mechanics. Thermody namic stability constants of the Cu(II) chelates was obtained by F-19-NMR. The synthesized Cu(II)-peptide chelates were tested as catalysts of some im portant red-ox processes occuring in biological systems, in particular oxid ation of ascorbate and dismutation of superoxide ion. The catalytic efficie ncy of the five chelates was much lower than that of ascorbate oxidase. On the contrary, two of them showed kinetic constants for superoxide dismutati on about one order of magnitude lower than that of the enzyme Cu,Zn superox ide dismutase. In both cases, the catalytic properties were dependent on th e peptide sequence. The relationships between structure and activity are di scussed to find the structural parameters crucial for catalytic activity th at can be modulated by appropriate design and synthesis of the peptides.