pH-tuned metal coordination and peroxidase activity of a peptide dendrimer enzyme model with a Fe(II)bipyridine at its core.

Peptide dendrimer BP1 was obtained by double thioether bond formation between 5,5'-bis(bromomethyl)-2,2'-bipyridine and two equivalents of peptide dendrimer N1 (Ac-Glu-Ser)(8)(Dap-Glu-Ala)(4)(Dap-Amb-Tyr)(2)Dap-Cys-Asp-NH(2) (Dap = branching 2,3-diaminopropanoic acid, Amb = 4-aminomethyl-benzoic acid). At pH 4.0 BP1 bound Fe(ii) to form the expected tris-coordinated complex [Fe(II)(BP1)(3)] (K(f) = 2.1 × 10(15) M(-3)). At pH 6.5 a monocoordinated complex [Fe(II)(BP1)] was formed instead (K(f) = 2.1 × 10(5) M(-1)) due to electrostatic repulsion between the polyanionic dendrimer branches, as confirmed by the behavior of three analogues where glutamates were partially or completely replaced by neutral glutamines or positive lysines. [Fe(II)(BP1)] catalyzed the oxidation of o-phenylenediamine with H(2)O(2) with enzyme-like kinetics (k(cat) = 1.0 min(-1), K(M) = 1.5 mM, k(cat)/k(uncat) = 90 000) and multiple turnover, while Fe(2+) or [Fe(bipy)(3)](2+) were inactive. The labile coordination positions allowing coordination to H(2)O(2) and to the substrate are likely responsible for the enhanced peroxidase activity of the metallopeptide dendrimer.