4N Complexes Research Articles

Ambivalent role of ascorbic acid in the metal-catalyzed oxidation of oligopeptides

The effect of ascorbic acid on the metal-catalyzed oxidation of a human prion protein model peptide has been studied. The complex formation of the peptide was clarified first. The studied model peptide contains a methionine and a histidine amino acids which are important both as binding sites for metal ions and sensitive parts of the protein for oxidation. pH-potentiometric, UV–Vis and circular dichroism spectroscopic techniques were applied to study the stoichiometry, stability and structure of the copper(II) complexes, while HPLC-MS and MS/MS were used for identifying the products of metal-catalyzed oxidation. 3N and 4N complexes with (Nim,N−,N−,S) and (Nim,N−,N−,N−) coordination modes are formed at pH 7.4, where the oxidation was studied. Singly, doubly and triply oxidized products are formed in which the methionine and/or the histidine side chain is oxidized. The oxidation was carried out with hydrogen peroxide solution by the addition of metal ions, namely copper(II) and iron(III) and/or ascorbic acid.

Crystal structure analysis of supramolecular arrangements in bis(1-isoquinolinecarboxamide)alkanes and their Ag(i) complexes

A homologous series of bis(1-isoquinolinecarboxamide)alkane derivatives (3a–f) with two to seven carbon atoms in the alkyl bridge and their Ag(I) complexes (4a–f) have been synthesized. Four ligand and five Ag(I) complex crystal structures were obtained by single crystal X-ray diffraction and analyzed in terms of: a) their structural patterns based on intra- and intermolecular hydrogen bonds which were compared to those of bis(2-quinolinecarboxamide)alkanes (1n) and bis(6-quinolinecarboxamide)alkanes (2n) attending to specific geometrical parameters and b) the Ag(I) coordinate bond effect on these patterns and the amide-to-amide hydrogen bonds. The crystal structures of the ligands 3a, 3c, 3d and 3e synthesized here show amide-to-amide interactions, the same as those occurring in the 2n derivatives, forming one or two-dimensional structures (β-sheets or 4,4-networks) via N–H⋯O(amide) hydrogen bonds. The coordinate bond in the 4n complexes predominates over the amide-to-amide hydrogen bond giving rise to structures ranging from discrete complexes to three-dimensional coordination polymers. Only the 4c complex merges supramolecular β-sheets connected by the silver coordination bonds.

The Coordination Abilities of New Cyclic Analogs of Somatostatin

Two new somatostatin analogs with a characteristic part of the sequence -c(Cys-Phe-Trp-Lys-Thr-Cys)- and with two histidine and two aspartic acid moieties in their structures were synthesized and analyzed in terms of their coordination abilities with copper (II) ions. Both peptides bind Cu(II) effectively. Ligands form 4N complexes with left{ {{text{N}}_{text{Im}} ,{ 3} {text{N}}_{text{amide}}^{ - } } right} binding mode in a basic range of pH. But in spite of very similar sequences of the two peptides a significant difference in the effectiveness of the binding of copper (II) ions was observed.

Modelling of copper(II) binding to pentapeptides related to atrial natriuretic factor using the 3χv connectivity index / Modeliranje vezivanja bakra(II) za pentapeptide povezane s atrijalnim natriuretičkim faktorom pomoću indeksa povezanosti 3χv

Abstract Using molecular graph theory we studied the binding of NSFRY-NH2 and 12 related pentapeptide amides to Cu(II) as a model system for atrial natriuretic factor (ANF) peptide interactions with copper. Linear regression models based on the valence connectivity index of the 3rd order (3χv) reproduced experimental stability constants (log β) for 1N, 2N, 3N, and 4N coordinated complexes with the standard error of 0.30-0.39 log β units. We developed separate models for seven tyrosinic (N=28) and five non-tyrosinic peptides (N=20), and a common model for both kinds of peptides (N=48) with an indicator (dummy) variable. The results indicate additional aromatic stabilisation in 4N complexes due to metal cation-π interactions with tyrosine but not with the phenylalanine residue. We have also amended the log K and log K* values to correct miscalculations published by Janicka-Klos et al. in 2013

Human annexins A1, A2, and A8 as potential molecular targets for Ni(II) ions.

Nickel is harmful for humans, but molecular mechanisms of its toxicity are far from being fully elucidated. One of such mechanisms may be associated with the Ni(II)-dependent peptide bond hydrolysis, which occurs before Ser/Thr in Ser/Thr-Xaa-His sequences. Human annexins A1, A2, and A8, proteins modulating the immune system, contain several such sequences. To test if these proteins are potential molecular targets for nickel toxicity we characterized the binding of Ni(II) ions and hydrolysis of peptides Ac-KALTGHLEE-am (A1-1), Ac-TKYSKHDMN-am (A1-2), and Ac-GVGTRHKAL-am (A1-3), from annexin A1, Ac-KMSTVHEIL-am (A2-1) and Ac-SALSGHLET-am (A2-2), from annexin A2, and Ac-VKSSSHFNP-am (A8-1), from annexin A8, using UV-vis and circular dichroism (CD) spectroscopies, potentiometry, isothermal titration calorimetry, high-performance liquid chromatography (HPLC), and electrospray ionization mass spectrometry (ESI-MS). We found that at physiological conditions (pH 7.4 and 37 °C) peptides A1-2, A1-3, A8-1, and to some extent A2-2 bind Ni(II) ions sufficiently strongly in 4N complexes and are hydrolyzed at sufficiently high rates to justify the notion that these annexins can undergo nickel hydrolysis in vivo. These results are discussed in the context of specific biochemical interactions of respective proteins. Our results also expand the knowledge about Ni(II) binding to histidine peptides by determination of thermodynamic parameters of this process and spectroscopic characterization of 3N complexes. Altogether, our results indicate that human annexins A1, A2, and A8 are potential molecular targets for nickel toxicity and help design appropriate cellular studies.

The impact of synthetic analogs of histidine on copper(II) and nickel(II) coordination properties to an albumin-like peptide. Possible leads towards new metallodrugs

The purpose of our research was to obtain peptidomimetics possessing Cu(II) and Ni(II) binding properties, which would be useful for biomedical applications. In this context we used potentiometry, UV–VIS and CD spectroscopies to characterize the Cu(II) and Ni(II) binding properties of pentapeptide analogs of the N-terminal sequence of histatin 5. The peptides investigated had a general sequence DSXAK-am (am stands for C-terminal amide), with X including His and its three synthetic analogs, (4-thiazolyl)-L-alanine (1), (2-pyridyl)-L-alanine (2), and (pyrazol-1-yl)-L-alanine (3). The heterocyclic nitrogens present in these analogs were significantly more acidic than that of the His imidazole. We found that DSXAK-am peptides were able to bind Cu(II) and Ni(II) and form 4N complexes in a cooperative fashion, with similar affinities. These results indicate that acidic heterocyclic amino acids provide a viable alternative for histidine in peptidomimetics designed for metal ion binding.

Sequence-specific Cu(II)-dependent peptide bond hydrolysis: similarities and differences with the Ni(II)-dependent reaction.

Potentiometry and UV-vis and circular dichroism spectroscopies were applied to characterize Cu(II) coordination to the Ac-GASRHWKFL-NH2 peptide. Using HPLC and ESI-MS, we demonstrated that Cu(II) ions cause selective hydrolysis of the Ala-Ser peptide bond in this peptide and characterized the pH and temperature dependence of the reaction. We found that Cu(II)-dependent hydrolysis occurs solely in 4N complexes, in which the equatorial coordination positions of the Cu(II) ion are saturated by peptide donor atoms, namely, the pyridine-like nitrogen of the His imidazole ring and three preceding peptide bond nitrogens. Analysis of the reaction products led to the conclusion that Cu(II)-dependent hydrolysis proceeds according to the mechanism demonstrated previously for Ni(II) ions (Kopera, E.; Krężel, A.; Protas, A. M.; Belczyk, A.; Bonna, A.; Wysłouch-Cieszyńska, A.; Poznański, J.; Bal, W. Inorg. Chem. 2010, 49, 6636-6645). However, the pseudo-first-order reaction rate found for Cu(II) is, on average, 100 times lower than that for Ni(II) ions. The greater ability of Cu(II) ions to form 4N complexes at lower pH partially compensates for this difference in rates, resulting in similar hydrolytic activities for the two ions around pH 7.

Pyrophosphate as a stabilizer of Ni(III) ions in aqueous solutions

Ni(II) ions in the presence of excess of pyrophosphate catalyze the decomposition of HSO5−, while forming relatively stable NiIII(P2O7)n3−4n complexes. Excess pyrophosphate stabilizes the trivalent nickel species, NiIII(P2O7)n3−4naq, i.e. increases considerably its lifetime.

Sialorphin and its analog as ligands for copper(II) ions

In this study the sialorphin (Gln-His-Asn-Pro-Arg) and its analog (Glp-His-Asn-Pro-Arg) were analyzed in terms of metal binding ability. Both peptides were synthesized using the solid-phase method. The application of number analytical methods: potentiometry, spectroscopy (UV–Vis, CD, NMR) and mass spectrometry allowed for a detailed characterization of the coordination abilities of presented peptides. The analysis of the obtained results has shown that both peptides are able to form a series of complexes. However due to the presence of free N-terminal amino group the sialorphin is more effective in metal ion binding. Nevertheless, in basic conditions both peptides involve the amide nitrogen belonging to the side chain of Asn3 moiety and form 4N complex with square planar structure. This unusual ability has been confirmed by the results obtained from the NMR studies.

Constructing optimal entanglement witnesses. II. Witnessing entanglement in4N×4Nsystems

We provide a class of optimal nondecomposable entanglement witnesses for 4N x 4N composite quantum systems or, equivalently, a new construction of nondecomposable positive maps in the algebra of 4N x 4N complex matrices. This construction provides natural generalization of the Robertson map. It is shown that their structural physical approximations give rise to entanglement breaking channels.

Sequence-Specific Ni(II)-Dependent Peptide Bond Hydrolysis for Protein Engineering: Reaction Conditions and Molecular Mechanism

Recently we screened a combinatorial library of R(1)-(Ser/Thr)-Xaa-His-Zaa-R(2) peptides (Xaa = 17 common alpha-amino acids, except Asp, Glu, and Cys; Zaa =19 common alpha-amino acids, except Cys; R(1) = CH(3)CO-Gly-Ala, R(2) = Lys-Phe-Leu-NH(2)) and established criteria for selecting Ser/Thr, Xaa, and Zaa substitutions optimal for specific R(1)-Ser/Thr peptide bond hydrolysis in the presence of Ni(II) ions (Krezel, A.; Kopera, E.; Protas, A. M.; Poznanski, J.; Wysłouch-Cieszynska, A.; Bal, W. J. Am. Chem. Soc. 2010, 132, 3355-3366). The screening results were confirmed by kinetic studies of hydrolysis of seven peptides: R(1)-Ser-Arg-His-Trp-R(2), R(1)-Ser-Lys-His-Trp-R(2), R(1)-Ser-Ala-His-Trp-R(2), R(1)-Ser-Arg-His-Ala-R(2), R(1)-Ser-Gly-His-Ala-R(2), R(1)-Thr-Arg-His-Trp-R(2), and R(1)-Thr-His-His-Trp-R(2). In this paper, we used the same seven peptides to investigate the molecular mechanism of the hydrolysis reaction. We studied temperature dependence of the reaction rate at temperatures between 24 and 75 degrees C, measured stability constants of Ni(II) complexes with hydrolysis substrates and products, and studied the course of R(1)-Ser-Arg-His-Trp-R(2) peptide hydrolysis under a broad range of conditions. We established that the specific square planar complex containing the Ni(II) ion bonded to the His imidazole nitrogen and three preceding peptide bond nitrogens (4N complex) is required for the reaction to occur. The reaction mechanism includes the N-O acyl shift, yielding an intermediate ester of R(1) with the Ser/Thr hydroxyl group. This ester hydrolyzes spontaneously, yielding final products. The Ni(II) ion activates the R(1)-Ser peptide bond by destabilizing it directly through peptide nitrogen coordination and, indirectly, by imposing a strain in the peptide chain.

Mononuclear copper(II) complexes of alloferons 1 and 2: A combined potentiometric and spectroscopic studies

Mononuclear copper(II) complexes of the alloferon 1 His-Gly-Val-Ser-Gly-His-Gly-Gln-His-Gly-Val-His-Gly, alloferon 2 Gly-Val-Ser-Gly-His-Gly-Gln-His-Gly-Val-His-Gly, Ac-alloferon 1 Ac-His-Gly-Val-Ser-Gly-His-Gly-Gln-His-Gly-Val-His-Gly and Ac-alloferon 2 Ac-Gly-Val-Ser-Gly-His-Gly-Gln-His-Gly-Val-His-Gly have been studied by potentiometric, UV–vis, CD and EPR spectroscopic methods. The potentiometric and spectroscopic data shows that acetylation of the amino terminal group induces significant changes in the coordination properties of the Ac-alloferons 1 and 2 compared to the alloferons 1 and 2, respectively. The presence of four (Ac-alloferon 1) or three (Ac-alloferon 2) histidyl residues provides a high possibility for the formation of macrochelates via the exclusive binding of imidazole-N donor atoms. The macrochelation suppresses, but cannot preclude the deprotonation and metal ion coordination of amide functions and the CuH −3L species with {N Im, 3N −} bonding mode at pH above 8 are formed. The N-terminal amino group of the alloferons 1 and 2 takes part in the coordination of the metal ion and the 4N complex with {NH 2, 3N Im} coordination mode dominates at physiological pH 7.4 for alloferon 1 and the 3N {NH 2, CO, 2N Im} binding mode for alloferon 2. However, at higher pH values sequential amide nitrogens are deprotonated and coordinated to copper(II) ions.

Resonant Raman study of local vibration modes in AlGaAsN layers

We report on resonant inelastic light scattering in dilute AlGaAsN films. Intense narrow peaks associated to N-related local vibration modes (LVM) have been observed around 325, 385, 400, 450, 500 and 540 cm −1. Their frequencies are compared to density functional theory supercell calculations of Al n Ga 4− n N complexes ( n=1−4). We find clear indications of the formation of Al 4N complexes. The values of the extended phonon frequencies reveal changes in the N distribution depending on the growth conditions. The LVM spectra are resonant in the energy range from 1.75 to 1.79 eV, which corresponds to an N-related electronic transition. Our results confirm the preferential bonding of N to Al in AlGaAsN.

Coordination abilities of α-synuclein fragments modified in the 30th (A30P) and 53rd (A53T) positions and products of metal-catalyzed oxidation

A potentiometric and spectroscopic (UV-Vis, CD and EPR) study of Cu(II) binding to the M26-D27-56 (A30P, A53T) and Ac-M26-D27-56 (A30P, A53T) fragments of α-synuclein was carried out. Mutations in the 30th (A30P) and 53rd (A53T) positions in these fragments do not change the binding mode of copper(II) ions but the stabilities of the 3N and 4N complexes formed for M26-D27-56 are lower compared to those of the M29-D30-56 peptide. At physiological pH 7.4 the 3N {NH2, N−, β-COO−, NIm} coordination mode dominates. The Ac-M26-D27-56 (A30P, A53T) fragment displays higher tendencies to aggregation than that of Ac-M29-D30-56. The high performance liquid chromatography (HPLC) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) methods and Cu(II)–hydrogen peroxide as a model oxidizing system to elucidate the products of copper(II)-catalyzed oxidation of the M26-D27-56 (A30P, A53T) fragment of α-synuclein were employed. A peptide solution (0.50 mM) was incubated at 37 °C for 24 h with a metal–peptide–hydrogen peroxide 1 : 1 : 4 molar ratio in a phosphate buffer, pH 7.4. Reaction of hydrogen peroxide with this fragment led to the oxidation of methionine to methionine sulfoxide. For the Cu(II)–peptide–hydrogen peroxide 1 : 1 : 4 molar ratio system oxidation of the histidine residue to 2-oxohistidine, asparagine and 5-hydroxy-2-oxohistidine was observed. Under experimental conditions the M26-D27-56 (A30P, A53T) fragment undergoes the fragmentations by cleavage of the V49–H50, H50–G51, G31–K32, T33–K34 and K43–T44 peptide bonds supporting the participation of the His and Lys residues in the coordination of copper(II) ions.

Copper(ii) binding by fragments of α-synuclein containing M1-D2- and -H50-residues; a combined potentiometric and spectroscopic study

Stability constants and ligand donor sets of the copper(II) complexes of the NH2-29-56(L1)(AA30GKTKEGVLYV40GSKTKEGVVH50GVATVA56-NH2), NH2-M29-D30-56(L2) and Ac-M29-D30-56(L3) fragments of alpha-synuclein were determined in aqueous solution for 1 : 1 metal-to-ligand molar ratio in the pH range 2.5-10.5. The tyrosine residue in the 39th position of the alpha-synuclein fragments does not take part in the coordination of the metal ion. The potentiometric and spectroscopic data (UV-Vis, CD, EPR) show that acetylation of the amino terminal group induces significant changes in the coordination properties of the L3 fragment compared to that of the L2 peptide. When the amino group is blocked (L3) the imidazole nitrogen of the histidine residue acts as an anchoring site and at higher pH the 3N {N(Im),2N-} and 4N {N(Im),3N-} complexes are formed. The L1 peptide at physiological pH forms in equilibrium 3N {NH2,N-,CO,N(Im)} and 4N {NH2,2N-,N(Im)} complexes. For the L2 peptide the coordination of the copper(II) ions starts from the N-terminal Met residue and with increasing of pH the Asp residue in second position of amino acid sequence coordinates and stabilizes significantly the 2N complex as a result of chelation through the beta-carboxylate group. At physiological pH the 3N {NH2,N-,beta-COO-,N(Im)} coordination mode dominates. At pH above 6 the results for the L2 fragment suggest the formation of 3N and 4N complexes (in equatorial plane) and the involvement of the lateral NH2 group of Lys residue in the axial coordination of Cu(II) ion. In CD spectra sigma (epsilon-NH2-Lys) --> Cu(II) charge transfer transition is observed. The stability constants for the L2 fragment of alpha-synuclein of the 4N {NH2,2N-,N(Im)} and {NH2,3N-} complexes are higher about 1.5 and 0.7 orders of magnitude, respectively, by comparison to those of the L1 peptide. This increase may be explained by the involvement of the epsilon-NH2 group of Lys residue in the coordination sphere of metal ion.

Coordination abilities of N-terminal fragments of α-synuclein towards copper(II) ions: A combined potentiometric and spectroscopic study

Copper(II) complexes of the 1–17 (MDVFMKGLSKAKEGVVA-NH 2), 1–28 (MDVFMKGLSKAKEGVVAAAEKTKQGVAE-NH 2), 1–39 (MDVFMKGLSKAKEGVVAAAEKTKQGVAEAPGKTKEGVLY-NH 2) and 1–39 (A30P) fragments of α-synuclein were studied by potentiometric, UV–Vis (UV–visible), CD (circular dichroism) and EPR (electron paramagnetic resonance) spectroscopic methods to determine the stoichiometry, stability constants and coordination modes of the complexes formed. The β-carboxylate group of Asp residue in second position of the peptide chain coordinates strongly to Cu(II) ion over the pH range 4–9.5 to give unusually stable 2N complex with {NH 2, N −, β-COO −, H 2O} coordination mode. At pH above 7 the results suggest the formation of 2N, 3N, 4N complexes (in equatorial plane) and the involvement of the lateral NH 2 group of Lys residue in the axial coordination of Cu(II) ion. In CD spectra σ ( ε-NH 2–Lys) → Cu(II) charge transfer transition is observed. Addition of the 18–28 and 18–39 fragments to the 1–17 peptide does not change the coordination mode and the 1–39 fragment forms the Cu(II) complexes with higher stabilities compared to those of the 1–17, 1–28 and 1–39(A30P) fragments of α-synuclein.

Copper(II) Interaction with Unstructured Prion Domain Outside the Octarepeat Region: Speciation, Stability, and Binding Details of Copper(II) Complexes with PrP106−126 Peptides

Copper(II) complexes of the neurotoxic peptide fragments of human and chicken prion proteins were studied by potentiometric, UV-vis, CD, and EPR spectroscopic and ESI-MS methods. The peptides included the terminally blocked native and scrambled sequences of HuPrP106-126 (HuPrPAc106-126NH2 and ScrHuPrPAc106-126NH2) and also the nona- and tetrapeptide fragments of both the human and chicken prion proteins (HuPrPAc106-114NH2, ChPrPAc119-127NH2, HuPrPAc109-112NH2, and ChPrPAc122-125NH2). The histidyl imidazole-N donor atoms were found to be the major copper(II) binding sites of all peptides; 3N and 4N complexes containing additional 2 and 3 deprotonated amide-N donors, respectively, are the major species in the physiological pH range. The complex formation processes for nona- and tetrapeptides are very similar, supporting the fact that successive deprotonation and metal ion coordination of amide functions go toward the N-termini in the form of joined six- and five-membered chelates. As a consequence, the peptide sequences investigated here, related to the neurotoxic region of the human PrP106-126 sequence, show a higher metal-binding affinity than the octarepeat fragments. In the case of the HuPrP peptide sequences, a weak pH-dependent binding of the Met109 residue was also detected in the 3N-coordinated complexes.

Nickel(II) binding to Cap43 protein fragments

Cap43 protein has been tested for metal binding domains. The protein, specifically induced by nickel compounds in cultured human cells, had a new mono-histidinic motif consisting of 10 amino acids repeated three times in the C-terminus. The 20-Ac-TRSRSHTSEG–TRSRSHTSEG (Thr341–Arg–Ser–Arg–Ser–His346–Thr–Ser–Glu–Gly–Thr–Arg–Ser–Arg–Ser–His356–Thr–Ser–Glu–Gly360 – peptide 1) and the 30–Ac-TRSRSHTSEG–TRSRSHTSEG–TRSRSHTSEG (Thr341–Arg–Ser–Arg–Ser–His346–Thr–Ser–Glu–Gly–Thr–Arg–Ser–Arg–Ser–His356–Thr–Ser–Glu–Gly–Thr–Arg–Ser–Arg–Ser–His366–Thr–Ser–Glu–Gly370 – peptide 2) amino acids sequence has been analyzed as a site for Ni(II) binding. A combined pH-metric and spectroscopic (UV–visible, CD, NMR) studies of Ni(II) binding to both fragments were performed. The 20-amino acid peptide can bind one and two metal ions while the 30-amino acid fragment one, two and three metal ions. At physiological pH, depending on the metal to ligand molar ratio, peptide 1 forms the Ni2L species while peptide 2 the NiL, Ni2L and Ni3L complexes where each metal ion is coordinated to the imidazole nitrogen atom of the histidine residue of the 10-amino acid fragment. Octahedral complexes at pH 8–9 and planar 4N complexes with (NIm, 3N−) bonding mode at pH above 9, are formed. This work supports the existence of an interesting binding site at the COOH-terminal domain of the Cap43 protein.

Nickel(II) binding to Cap43 protein fragments

Cap43 protein has been tested for metal binding domains. The protein, specifically induced by nickel compounds in cultured human cells, had a new mono-histidinic motif consisting of 10 amino acids repeated three times in the C-terminus. The 20-Ac-TRSRSHTSEG–TRSRSHTSEG (Thr 341–Arg–Ser–Arg–Ser–His 346–Thr–Ser–Glu–Gly–Thr–Arg–Ser–Arg–Ser–His 356–Thr–Ser–Glu–Gly 360 – peptide 1) and the 30–Ac-TRSRSHTSEG–TRSRSHTSEG–TRSRSHTSEG (Thr 341–Arg–Ser–Arg–Ser–His 346–Thr–Ser–Glu–Gly–Thr–Arg–Ser–Arg–Ser–His 356–Thr–Ser–Glu–Gly–Thr–Arg–Ser–Arg–Ser–His 366–Thr–Ser–Glu–Gly 370 – peptide 2) amino acids sequence has been analyzed as a site for Ni(II) binding. A combined pH-metric and spectroscopic (UV–visible, CD, NMR) studies of Ni(II) binding to both fragments were performed. The 20-amino acid peptide can bind one and two metal ions while the 30-amino acid fragment one, two and three metal ions. At physiological pH, depending on the metal to ligand molar ratio, peptide 1 forms the Ni 2L species while peptide 2 the NiL, Ni 2L and Ni 3L complexes where each metal ion is coordinated to the imidazole nitrogen atom of the histidine residue of the 10-amino acid fragment. Octahedral complexes at pH 8–9 and planar 4N complexes with (N Im, 3N −) bonding mode at pH above 9, are formed. This work supports the existence of an interesting binding site at the COOH-terminal domain of the Cap43 protein.

Copper(II) and zinc(II) complexes of the peptides Ac-HisValHis-NH2 and Ac-HisValGlyAsp-NH2 related to the active site of the enzyme CuZnSOD

Copper(II) and zinc(II) complexes of the peptides Ac-HisValHis-NH2 and Ac-HisValGlyAsp-NH2 related to the active site of the enzyme CuZnSOD were studied by potentiometric and spectroscopic (UV–Vis, CD and EPR) techniques. The results reveal that both ligands have effective metal binding sites, but the tripeptide is a much stronger complexing agent than the tetrapeptide. The formation of a macrochelate via the coordination of the imidazolyl residues is suggested in the copper(II)–Ac-HisValHis-NH2 system in the acidic pH range, while a 4N complex predominates at physiological pH. The interaction of Ac-HisValHis-NH2 with zinc(II) results in the formation of a precipitate indicating polynuclear complex formation. Both copper(II)–Ac-HisValHis-NH2 and copper(II)–HisValHis systems exhibit catalytic activity toward the dismutation of superoxide anion at physiological pH, but the saturated coordination sphere of the metal ions in both systems results in low reactivity as compared to the native enzyme.