Cupric ion complexes of histidine-containing peptides.

The binding of cupric or zinc ion by sperm whale metmyoglobin appears to involve imidazole groups of histidyl residues (4, 5) that occur well removed from the NH2 terminus (6). The binding of each cupric ion by metmyoglobin is accompanied on the average by the displacement of one or more protons beyond that that may be borne by the imidazole group, presumably from peptide amide nitrogen atoms (4, 5). Such displacement of amide protons is best known for simple peptides containing a free terminal amino group (1, 7-10). Histidine-containing peptides lacking a free terminal amino group have been studied very little, except for one in which flexibility is probably quite restricted (11). For these reasons, the observations with metmyoglobin have remained unparalleled with model peptide systems (4, 12). The present paper deals with complex formation between cupric ions and a number of histidine-containing peptides including a series of peptides of the form acetyl(glycyl),-L-histidine, acetylglycyl-L-histidylglycine, and some of the corresponding peptides lacking the terminal acetyl group. The results show that the longer acetylated histidine-containing peptides react with cupric ions to form 1:l complexes that dissociate protons in comparable number and in a comparable pH range to the cupric ion complexes of metmyoglobin or apomyoglobin.