Grazyna Formicka-Kozlowska

EPR, NMR and absorption spectroscopy studies of Ni(II) and Cu(II) complexes with Thr-Lys-Ala-Ala peptide in aqueous solution

Abstract The PMR, EPR and absorption spectroscopy methods have been used to propose the structure of Ni(II) and Cu(II)ThrLysAlaAla complexes formed in the aqueous solution over a broad pH range. The binding sites in tetrapeptide to both metal ions are shown to be the NH2-Thr, and three deprotonated nitrogens of peptide linkages. In the case of Ni(II) ions the cooperative interaction was observed.

Copper (II) interaction with proline-containing tetrapeptides

Abstract The Cu(II) interactions with four tetrapeptides: Ala-Ala-Ala-Ala, Ala-Ala-Ala-Pro, Ala-Ala-Pro-Ala, and Pro-Ala-Ala-Ala were studied by the absorption, circular dichroism, and electron paramagnetic resonance spectra. The results clearly show that proline residue is a specific structural factor in the formed complexes and, on the other hand, it is a break point in the metal ion coordination to the consecutive peptide bond nitrogens. The only position of proline residue ina peptide sequence that makes proline nitrogen available for the metal ion coordination is the N-terminal position. But even in this case (i.e., in the Cu(II) Pro-Ala-Ala-Ala system) proline plays a critical role in the creation of the specific structures in the complex formed in solution.

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

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.

Coordination ability of the thyrotropin releasing factor, l-pyroglutamyl-l-histidyl-l-prolinamide(TRF).III. Cu(II) and Ni(II) complexes with TRF and its di- and tripeptide analogues

Abstract The results are reported of a spectroscopic and potentiometric study of the copper(II) and nickel(II) complexes of the thyrotropin releasing factor (L-pyroglutamyl-L-histidyl-L-prolinamide, TRF) and some of its di- and tripeptide analogues Spectroscopic techniques used include absorption, circular dichroism and electron paramagnetic resonance spectroscopy TRF and pyroglutamyl-histidine behave similarly. At low pH the metal ions coordinate to the imidazole nitrogen and then cause the ionization of the amide protons of both the peptide linkage and the pyroglutamic acid with equal ease. Hence the concentration of MH −1 L species is always very low. The C-terminal proline amide residue plays an insignificant role in the complex formation Replacement of pyroglutamic acid with picolinic acid in the hormone molecule causes a major change in the structures of its complexes. The dipeptide analogue, Pic-His. forms dimeric species with Cu(II) that are not found in Cu(II) Pyr-His orCu(II) TRF solutions The introduction of tyrosine residue in the TRF sequence in place of histidine can, in some cases, lead to the direct involvement of proline amide in the binding of metal ions, e.g. , Ni(II) Pyr-Tyr-Pro-NH 2

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

The L-proline residue in oligopeptides has been shown to act as a ‘break-point’ in their co-ordination to copper(II) ions leading to the formation of large chelate rings with the peptide locked in the β-conformation.

The coordination of copper(II) with β-casomorphin and its fragments

The synthesis of β-casomorphin-5 (Tyr-Pro-Phe-Pro-Gly, H2L) and a number of its peptide fragments is described. Complexes formed between these peptides and Cu(II) have been investigated spectrophotometrically, using CD and EPR spectroscopy, and potentiometrically. Results show that, with tyrosine as the N-terminal residue, the major complex formed at physiological pH is the dimeric species, [Cu2L2], bonded through the phenolic O− of the Tyr residue of one ligand and the N-terminal amine nitrogen of the second ligand molecule. There is no evidence for coordination through the peptide nitrogens unless the terminal Tyr group is removed.

NMR and EPR study of the Cu(II)-glutathione interaction in water solution

Abstract NMR, EPR and absorption spectra were used to study the interaction between the copper(II) ion and glutathione over a wide pH range. The coordination sites of the Cu(II) ion in glutathione peptide were established with NMR method. EPR reveals two non-equivalent metal ions coordinated to the peptide in basic solutions for molar ratios Cu: glutathione greater than 1. Structures for the Cu(II) glutathione complex for different meta-peptide molar ratios were assumed. The character of the metal-peptide bonding was inferred from the EPR data.

Coordination ability of the thyrotropin releasing factor. II. Nickel(II) complexes with TRF

Abstract The interactions of Ni(II) with PyrHisProNH 2 (TRF) and PyrHis dipeptide analogue have been studied with use of absorption and CD spectroscopy as well as the 1 H NMR spectra. The formation of two planar complexes characterized by different CD spectra has been found in basic solutions. In both planar species the coordination sites are three nitrogen donors i.e. N 3 of imidazole, N − of the peptide linkage between Pyr and His residues and N − of Pyr residue. The difference in CD spectra of two planar complexes has been explained in terms of chelate ring conformation change due to the deprotonation of N1 imidazole nitrogen. The N1 deprotonation is promoted by the Ni(II) coordination to N3 nitrogen of imidazole ring.

A potentiometric and spectroscopic study of the proton and copper(II) complexes of methionine enkephalin and some related ligands

The results are reported of a potentiometric and spectrophotometric study of the proton and copper(II) complexes of methionine enkephalin and four related pentapeptides which all show greater biological activity than their parent enkephalin. Measurements were carried out at 25 degrees C and I = 0.10 mol dm-3 (KNO3). All the ligands studied form stable copper(II) complexes comparable to those formed by pentaglycine, with the peptide chain locked in a folded conformation by NNN or NNNN coordination to the metal ion. There is no indication of bonding through the tyrosine-phenolate oxygen atoms or the methionine sulfurs.

Effect of side amino acid groups on the effectiveness of nitric oxide binding by the cobalt complexes with amino acids

Abstract The effect of metal environment on the effectiveness of nitric oxide binding by the cobalt complexes with amino acids and with amino acids and imidazole was investigated. The results of spectroscopic studies and magnetic moment measurements (NMR) indicate an equilibrium in solution between the active cobalt(II) complex and the nitrosyl cobalt(III) complex.