Imre Sóvágó

CRITICAL SURVEY OF STABILITY CONSTANTS OF COMPLEXES OF GLYCINE

Chairman: 1987-89 L. D. Pettit (UK); 1989-91 D. G. Tuck (Canada); Secretary: 1987-89 0. Yamauchi (Japan); 1989-91 T. Kiss (Hungary); Titular Members: A. C. M. Bourg (1989-91; France); A. Braibanti (1987-91; Italy); H. K. J. Powell (1989-91; New Zealand); D. G. Tuck (1987-89; Canada); P. Valenta (1987-89; FRG); Associate Members: A. C. M. Bourg (198789; France); R. H. Byrne (1989-91; USA); I. R. Grenthe (1987-89; Sweden); B. Holmberg (1987-91; Sweden); S. Ishiguro (1989-91; Japan); T. A. Kaden (1987-91; Switzerland); T. Kiss (1987-89; Hungary); S. H. Laurie (1989-91; UK); P. A. Manorik (1987-91; USSR); R. B. Martin (1987-91; USA); P. Paoletti (1987-91; Italy); R. Portanova (1987-91; Italy); H. J. K. Powell (1987-89; New Zealand); S. Sjoberg (1989-91; Sweden); National Representatives: M. P. Zhang (1989-91; Chinese Chemical Society); P. Valenta (1989-91; FRG); L. H. J. Lajunen (1987-91; Finland); M. T. Beck (1987-91; Hungary); P. K. Bhattacharya (1987-91; India); H. Ohtaki (1987-91; Japan); C. Luca (1987-89; Romania); S. Ahrland (1987-91; Sweden); I. Tor (1989-91; Turkey); L. D. Pettit (1989-91; UK); G. R. Choppin (1987-89; USA); K. I. Popov

Critical survey of the stability constants of complexes of aliphatic amino acids (Technical Report)

Stability constants for the proton and metal ion complexation equilibria of aliphatic amino acids including a-alanine, valine, 2-aminopentanoic acid, leucine, isoleucine, 2-aminohexanoic acid and 8-alanine were collected and critically evaluated. Data evaluation criteria involved the specification of the essential reaction conditions, the correctness of calibration techniques and calculation and the applicability of the methods used for the determination of stability constants. Recommended values for the proton and some metal ion complexes are collected in separate tables. Enthalpy values published on the protonation equlibria and metal ion complex formation processes of aliphatic amino acids were also surveyed.

EPR and potentiometric reinvestigation of copper(II) complexation with simple oligopeptides and related compounds

Abstract The coordination modes of Cu(II) to Di-, Tri-, and Tetra-glycine and related ligands were investigated, within the entire measurable pH range and over a wide range of ligand excess, by means of electron paramagnetic resonance, electron spectroscopy, and in some cases, pH potentiometry. The results, besides allowing the identification of the complex species involved and the attribution of distinctive spectral data set to the various structures, provide significant insight in relation to: i) the coordination ability of the zwitterionic AH form of simple oligopeptides to yield COO − - or 2COO − -complexes or species with mixed [(NH 2 , CO)(COO − )] or [(NH 2 , N − , COO − )(COO − )] coordination; ii) the influence of the size of the (NH 2 , CO), (NH 2 , N − ), and (N − , COO − ) chelated rings on the stability and structure of the complex species; iii) the bis-complex formation processes taking place with Gly-β-ala, β-Alagly, Tri-, and Tetraglycine.

The Metal Loading Ability of β-Amyloid N-Terminus: A Combined Potentiometric and Spectroscopic Study of Copper(II) Complexes with β-Amyloid(1−16), Its Short or Mutated Peptide Fragments, and Its Polyethylene Glycol (PEG)-ylated Analogue

Alzheimers disease (AD) is becoming a rapidly growing health problem, as it is one of the main causes of dementia in the elderly. Interestingly, copper(II) (together with zinc and iron) ions are accumulated in amyloid deposits, suggesting that metal binding to Abeta could be involved in AD pathogenesis. In Abeta, the metal binding is believed to occur within the N-terminal region encompassing the amino acid residues 1-16. In this work, potentiometric, spectroscopic (UV-vis, circular dichroism, and electron paramagnetic resonance), and electrospray ionization mass spectrometry (ESI-MS) approaches were used to investigate the copper(II) coordination features of a new polyethylene glycol (PEG)-conjugated Abeta peptide fragment encompassing the 1-16 amino acid residues of the N-terminal region (Abeta(1-16)PEG). The high water solubility of the resulting metal complexes allowed us to obtain a complete complex speciation at different metal-to-ligand ratios ranging from 1:1 to 4:1. Potentiometric and ESI-MS data indicate that Abeta(1-16)PEG is able to bind up to four copper(II) ions. Furthermore, in order to establish the coordination environment at each metal binding site, a series of shorter peptide fragments of Abeta, namely, Abeta(1-4), Abeta(1-6), AcAbeta(1-6), and AcAbeta(8-16)Y10A, were synthesized, each encompassing a potential copper(II) binding site. The complexation properties of these shorter peptides were also comparatively investigated by using the same experimental approach.

Interaction of copper(II) with the prion peptide fragment HuPrP(76-114) encompassing four histidyl residues within and outside the octarepeat domain.

Complex formation processes between the 39-mer residue peptide fragment of human prion protein, HuPrP(76-114), and copper(II) ions have been studied by potentiometric, UV-vis, circular dichroism (CD), electron paramagnetic resonance, and electrospray ionization mass spectrometry methods. This peptide consists of 39 amino acid residues and contains two histidines (His77 and His85) belonging to the octarepeat domain and two histidines (His96 and His111) outside this domain. It was found that HuPrP(76-114) is able to bind 4 equiv of metal ions and all histidyl residues are independent, except nonequivalent metal binding sites in the oligonuclear species. Imidazole nitrogen donor atoms are the primary and exclusive metal binding sites below pH 5.5 in the form of various macrochelates. The macrochelation slightly suppresses, but cannot prevent, the deprotonation and metal ion coordination of amide functions, resulting in the formation of (N(im),N(-)), (N(im),N(-),N(-)), and (N(im),N(-),N(-),N(-))-coordinated copper(II) complexes in the pH range from 5.5 to 9. CD spectroscopy results gave clear evidence for the differences in the metal binding affinity of the histidyl sites according to the following order: His111 > His96 >> His77 approximately His85. Among the oligonuclear complexes, the formation of di- and tetranuclear species seems to be favored over the trinuclear ones, at pH values beyond the physiological ones. This phenomenon was not observed in the complex formation reactions of HuPrP(84-114), a peptide fragment containing only one histidyl residue from the octarepeat. As a consequence, the data support the existence of cooperativity in the metal binding ability of this peptide probably due to the presence of two octarepeat sequences of the dimeric octarepeat domain of HuPrP(76-114) at basic pH values.

Metal Loading Capacity of Aβ N-Terminus: a Combined Potentiometric and Spectroscopic Study of Zinc(II) Complexes with Aβ(1−16), Its Short or Mutated Peptide Fragments and Its Polyethylene Glycol−ylated Analogue

Aggregation of the amyloid beta-peptide (Abeta) into insoluble fibrils is a key pathological event in Alzheimers Disease (AD). There is now compelling evidence that metal binding to Abeta is involved in AD pathogenesis. The amino acid region 1-16 is widely considered as the metal binding domain of Abeta. In this work, we used a combined potentiometric, NMR, and electrospray ionization mass spectrometry (ESI-MS) approach to study the zinc(II) binding to a new polyethylene glycol (PEG)-conjugated peptide fragment encompassing the 1-16 amino acid sequence of Abeta (Abeta(1-16)PEG). Our results demonstrate for the first time that the Abeta(1-16) is able to coordinate up to three zinc ions, all the histidyl residues acting as independent anchor sites. The study was complemented by systematically investigating the zinc(II) complexes of a series of shorter peptide fragments related to the Abeta(1-16) sequence, namely, Abeta(1-4), Abeta(1-6), AcAbeta(1-6), AcAbeta(8-16)Y10A. The comparison of the whole results allowed the identification of the zinc(II) preferred binding sites within the longer Abeta(1-16) amino acid sequence. Unlike copper(II) that prefers the N-terminal amino group as the main binding site, the zinc(II) is preferentially placed in the 8-16 amino acidic region of Abeta(1-16).

Interaction of Cu2+ with His–Val–His and of Zn2+ with His–Val–Gly–Asp, two peptides surrounding metal ions in Cu,Zn-superoxide dismutase enzyme

His-Val-His and His-Val-Gly-Asp are two naturally occurring peptide sequences, present at the active site of Cu,Zn-superoxide dismutase (Cu,Zn-SOD). The interactions of His-Val-His=A (copper binding site) with Cu(II) and of His-Val-Gly-Asp=B (zinc binding site) with Zn(II) have been studied by using both potentiometric and spectroscopic methods (visible, EPR, NMR). The stoichiometry, stability constants and solution structure of the complexes formed have been determined. The binding modes of the species [CuAH](2+) and [CuA](+) were characterized by histamine type of coordination. [CuA](+) is further stabilized by the formation of a macrochelate with the involvement of the imidazole of the C-terminal histidine. The existence of macrochelate results in a slight distortion of the coordination geometry providing good base for the development of enzyme models. The enhanced stability of the macrochelate suppresses the formation of bis-complexes as well as the amide deprotonation. This process, however, takes place at higher pH resulting in the formation of the 4 N(-) coordinated [NH(2),N(-),N(-),N(im)] species [CuAH(2-)](-). On the other hand, in the case of the Zn(II)-His-Val-Gly-Asp system, coordination takes place at the terminal carboxylate in species [ZnBH(2)](2+). Monodentate binding occurs via the N-terminal imidazole in [ZnBH](+) while histamine type of coordination is possible in [ZnB], [ZnB(2)H](-) and [ZnB(2)](2-) species. Amide deprotonation does not take place in the case of Zn(2+), hydroxo-complexes are formed instead.

Studies on transition-metal–peptide complexes. Part 9. Copper(II) complexes of tripeptides containing histidine

Copper(II) complexes of the histidine-containing tripeptides glyclyl-L-histidylglycine (GlyHisGly), glycylglycyl-L-histidine (GlyGlyHis), and L-pyroglutamyl-L-histidyl-L-prolinamide (trf), and the dipeptide L-pyroglutamyl-L-histidine methyl ester (pghme), have been studied by pH-metric and spectrophotometric methods. It was found that, similarly as for glycyl-L-histidine (GlyHis), GlyHisGly forms a complex [CuAH–1], but bis complexes are also formed in low concentration. For GlyGlyHis, only the highly stable species [CuAH–2]– is formed. A complex [CuAH–2]– is also formed with trf and pghme which indicates that the prolinamide side-chain in trf does not take part in the co-ordination. The sequence of deprotonation of the N1H group of the imidazole side-chain is as follows: GlyHisGly > GlyHis > pghme > trf > GlyGlyHis.

Cadmium ion interaction with sulphur containing amino acid and peptide ligands

Abstract Cadmium complexes of 15 ligands containing sulphur donors in various environments were studied by potentiometric and polarographic methods. Thiol donors were the most effective in cadmium binding in the order of (S,N,O) > (S,N) > (S,O,O) > (S,O) donor sets. Thioamide groups also enhance the stability of the complexes formed, while the disulphide group is ineffective in the presence of amino acid or peptide binding sites.

Transition metal complexes of L-cysteine containing di- and tripeptides.

Nickel(II), cobalt(II), zinc(II), and cadmium(II) complexes of Ala-Cys, Phe-Cys, and Ala-Ala-Cys were studied by potentiometric and spectroscopic methods. Ni(II) induces deprotonation and coordination of the amide nitrogens, and the stable monomeric or oligomeric complexes are formed, depending on the metal to ligand molar ratios. Formation of the stable bis-complexes with [S,O] coordination mode is characteristic for cobalt(II), zinc(II), and cadmium(II) ions.