Hemopressin is a
neuropeptide, derived from the degradation of the α(1)-chain of
hemoglobin, and possesses several pharmacologic properties, such as the ability to block
cannabinoid CB1 receptor activity, to cause dose-dependent
hypotension and to inhibit food intake. Actually, human
hemopressin (PVNFKLLSH) is only the precursor of a class of longer
peptides, called "Pepcans", which bear additional residues at their amino-terminus and possess slightly different chemical and
biological properties with respect to
hemopressin. The presence of a histidyl residue and the free terminal
amine imparts to
hemopressin and its derivatives good binding properties towards transition
metal ions. In this paper, we present a wide investigation on the complex-formation equilibria of human
hemopressin and three analogues towards the Cu(ii) and Ni(ii)
ions. The study showed that the main coordination site is always the amino terminus (if not protected), while the C-terminal
histidine acts only as an anchoring site for the
metal ions at acidic pH, with the formation of a macrochelate complex. The presence of additional residues in N-terminal position produces significant differences in the protonation and complex-formation behaviors of these
peptides, which can be explained in terms of charge of the
ligand and coordination environment. Although the participation of
metal ions in the
biological activity of
hemopressin and Pepcans has not yet been demonstrated, the data reported here can help to shed light on the mechanisms governing the action of these
neuropeptides in vivo.