Transport of Cu(II) from an albumin mimic peptide, GlyGlyHisGly, to histidine and penicillamine

Cu in blood has been believed to transport into cell via albumin and some amino acids. To shed light on the Cu transport process we studied the reaction of the Cu(II)-peptide with the amino acid by absorption and CD spectra. Albumin mimic peptides GlyGly-l-HisGly (GGHG) and penta-Gly(G5) formed stable 4N coordinated Cu(II) complexes, but in the reaction with histidine (His) and penicillamine (Pes) the ternary Cu(II) complex formations were observed different by the kinetic study. Cu(II)-G5 complexes reacted with Pes to form the ternary complex Cu(H−1G5)(Pes−) which was subsequently transformed to the binary complex Cu(Pes−)2. In the system with GGHG the Cu(II) was also transported from GGHG to Pes, but the ternary Cu(H−1GGHG)(Pes−) complex as the intermediate was detected a trace. The ternary complex would be spontaneously transformed to Cu(Pes−)2 upon forming, because the rate constant of the ternary complex formation k1+ = ∼2 M−1 s−1 was less than k2+ = ∼5 × 102 M−1 s−1 for the Cu(Pes−)2 formation at physiological pH. In the Cu(II)-GGHG-His system the ternary Cu(H−1GGHG)(His) complex was also hardly identified because the formation constant K1 and k1+ were very small and the equilibrium existed between Cu(H−2GGHG) and Cu(His)2 and its overall equilibrium constant β2 for Cu(His)2 was very small to be 1.00 ± 0.05 M−1 at pH 9.0. These results indicated that the ternary complex is formed in the Cu transport process from the albumin to the amino acid, but His imidazole nitrogen in the fourth-binding site of Cu(II) strongly resists the replacement by the incoming ligand.