The L-proline residue as a ‘break-point’ in metal–peptide systems

Abstract

Results are reported of a potentiometric and spectrophotometric study of the H⁺ and Cu²⁺ complexes of the tetrapeptides X-Gly-Gly-Gly, Gly-X-Gly-Gly, Gly-Gly-X-Gly, and Gly-Gly-Gly-X where X is the proline (Pro) and sarcosine (Sar) residue (Gly = glycine). All the tetrapeptides (HL) form the series of complexes [CuL], [CuH_–1L], [CuH_–2L], and [CuH_–3L](charges omitted). The ligands Gly-X-Gly-Gly also form the bis-complex, [CuL₂]. When inserted in a peptide chain the Pro and Sar residues cannot co-ordinate to Cu²⁺ through their peptide nitrogens since they do not possess ionizable protons. In addition the Pro residue tends to force the peptide chain to form a ‘β-turn’ and so adopt a ‘bent’ conformation. These studies demonstrate the formation of a large chelate ring when tetrapeptides containing Pro (and, to a smaller extent, Sar) in the second or third positions co-ordinate to Cu²⁺. This ring spans the terminal residues of the peptide chain and locks the peptide into a ‘bent’ or ‘horse-shoe’ shaped conformation. Cu²⁺ could therefore play an important role in activating oligopeptides (e.g. neuropeptides) containing proline.