Molecular design to mimic the copper(II) transport site of human albumin. The crystal and molecular structure of copper(II) – glycylglycyl-L-histidine-N-methyl amide monoaquo complex

Abstract

Glycylglycyl-L-histidine-N-methyl amide is a copper-binding tripeptide designed and synthesized to mimic the copper-transport site of human albumin. Reddish-purple crystals of the copper-tripeptide amide complex (Cu–GGHa), grown at physiological pH, are triclinic, with cell dimensions a = 9.990, b = 9.986, c = 7.682 Å, α = 107.40, β = 91.72, γ = 96.49°, space group P1, Z = two units of Cu–GGHa and two water molecules per cell. The structure was solved by interpretation of a Cu–phased Fourier map containing a great deal of false symmetry, after multiple attempts with direct phasing methods failed. Refinement proceeded to R = 0.036. The conformations of the two Cu–GGHa units are virtually identical. Each copper is tetradentate chelated by the amino terminal nitrogen, the next two peptide nitrogens, and a histidyl nitrogen of a single tripeptide molecule in a mildly distorted square planar arrangement. The Cu…N distances range between 1.90–2.05 Å, with N…Cu…N angles of 165 and 176°. An oxygen atom provides a fifth position weaker interaction in each case, with Cu…O distances of 2.61 and 2.88 Å.