Vanadium(III) binding strengths of small biomolecules

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Copper(II), nickel(II) and zinc(II) complexes of hexapeptides containing separate aspartyl and histidyl residues

Copper(II), nickel(II) and zinc(II) complexes of two N-terminally free and C-terminally blocked hexapeptides, NH2-ADAAAH-NH2 and NH2-AADAAH-NH2, containing separate aspartyl and histidyl residues have been studied by potentiometric, UV-Vis, CD and ESR spectroscopic methods. The amino termini were found as the primary anchoring sites of both ligands for the complexation with all three metal ions. The β-carboxylate function of the second or third aspartyl residue enhances the thermodynamic stability of the copper(II) and nickel(II) complexes and shifts the deprotonation of the subsequent amide functions into a more alkaline pH range. In the case of NH2-AADAAH-NH2 the imidazole-N donor of the histidyl residue does not have a significant contribution to the overall stability of the mononuclear complexes. The side chain imidazole, however, can be an independent metal binding site resulting in the formation of dinuclear or even mixed metal complexes. The stabilizing role of the histidyl residue is much more pronounced in the complexes of the NH2-ADAAAH-NH2 peptide. In this case a tridentately (NH2,N-,β-COO-)-coordinated species is formed and its stability is significantly enhanced by the macrochelation of the side chain imidazole. The presence of two anchoring sites (terminal amino and side chain imidazole) in one molecule enhances the stability of the corresponding zinc(II) complexes, too, but the amide nitrogens are not involved in metal binding in this case

Interaction of Cu(II)with His-Val-Gly-Asp and of Zn(II) with His-Val-His, Two Peptides at the Active Site of Cu,Zn-Superoxide Dismutase

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). We have already studied the interaction of His-Val-His=A (copper binding site) with Cu(II) and of His-Val-Gly-Asp=B (zinc binding site) with Zn(II). As a continuation of this work and for comparison purposes we have also studied the interaction of Zn(II) with His-Val-His and Cu(II) with His-Val-Gly-Asp using both potentiometric and spectroscopic methods (visible, EPR, NMR). The stoichiometry, stability constants and solution structure of the complexes formed have been determined. Histamine type of coordination is observed for/ZnAH/2+, /ZnA/+, /ZnA2H/+ and/ZnA2/ in acidic pH while deprotonation of coordinated water molecules is observed at higher pH. /CUB/ species is characterized by the formation of a macrochelate and histamine type coordination. Its stability results in the suppression of amide deprotonation which occurs at high pH resulting in the formation of the highly distorted from square planar geometry 4N complex/CuBH-3/3

Unusual binding modes in the copper(II) and palladium(II) complexes of peptides containing both histidyl and cysteinyl residues

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Complex formation processes and metal ion catalyzed oxidation of model peptides related to the metal binding site of the human prion protein

Interaction of copper(II) and nickel(II) ions with the Ac-PHAAAGTHSMKHM-NH2 tridecapeptide containing the His85, His96 and His111 binding sites of human prion protein has been studied by various techniques. pH-potentiometry, UV-Vis and circular dichroism spectroscopy were applied to study the stoichiometry, stability and structure of the copper(II) and nickel(II) complexes, while HPLC-MS and MS/MS were used for identifying the products of copper(II) catalyzed oxidation. The copper binding ability of shorter fragments, namely the nonapeptide Ac-PHAAAGTHS-NH2 and pentapeptide Ac-PHAAA-NH2 have also been studied. The tridecapeptide is able to bind three equivalent of copper(II) ion, since the histidine residues behave as independent metal binding sites. Nevertheless, the metal binding ability of histidine residue mimicking the octarepeat domain (His85) is decreased, while the other parts of the peptide mimicking the histidines outside the octarepeat domain bind the copper ions in comparable concentration. On the other hand, this peptide is able to coordinate only two equivalents of nickel ion on the domains outside the octarepeat region. Furthermore the His96 binding site is more effective for the nickel ions. Both histidine and methionine residues are sensitive for oxidation, the oxidation of these residues are proved, and in the case of the histidine residues follows the order His96 >His85 >> His111

Thermodynamic and Structural Characterization of the Copper(II) Complexes of Peptides Containing Both Histidyl and Aspartyl Residues

Terminally protected pentapeptides with 2 histidines (Ac-HHVGD-NH2 and Ac-HVGDH-NH2) and the terminally free peptides containing both internal aspartyl and C-terminal histidyl residues (FDAH and VIDAH) have been synthesized, and copper(II) complexes studied by potentiometric, UV-Vis, CD, and EPR spectroscopic techniques in solution. Both thermodynamic and spectroscopic data reveal that side chain donor atoms of aspartyl and histidyl residues have a significant contribution to the metal binding affinity of peptide molecules. In the case of terminally protected peptides, the role of the imidazole-N donor functions is reflected in the enhanced stability of the 3N and 4N coordinated copper(II) complexes. The amino and β-carboxylate groups of FDAH and VIDAH create a very effective metal binding site with the (NH2, N−, β-COO−) and (NH2, N−, N−, β-COO−) coordination modes including the N-termini, while the histidine sites are available for the formation of the (Nim, N−, N−) binding mode resulting in the preference of dinuclear complex formation

Potentiometric and spectroscopic studies on the copper(ii) complexes of rat amylin fragments. The anchoring ability of specific non-coordinating side chains.

Copper(ii) complexes of peptides modelling the sequence of the 17-22 residues of rat amylin have been studied by potentiometric, UV-Vis, CD and ESR spectroscopic methods. The peptides were synthesized in N-terminally free forms, NH2-VRSSNN-NH2, NH2-VRSSAA-NH2, NH2-VRAANN-NH2, NH2-VRSS-NH2, NH2-SSNN-NH2, NH2-SSNA-NH2 and NH2-AANN-NH2, providing a possibility for the comparison of the metal binding abilities of the amino terminus and the -SSNN- domain. The amino terminus was the primary ligating site in all cases and the formation of only mononuclear complexes was obtained for the tetrapeptides. The thermodynamic stability of the (NH2, N-, N-) coordinated complexes was, however, enhanced by the asparaginyl moiety in the case of NH2-SSNN-NH2, NH2-SSNA-NH2 and NH2-AANN-NH2. Among the hexapeptides the formation of dinuclear complexes was characteristic for NH2-VRSSNN-NH2 demonstrating the anchoring ability of the -SSNN- (SerSerAsnAsn) domain. The complexes of the heptapeptide NH2-GGHSSNN-NH2 were also studied and the data supported the above mentioned anchoring ability of the -SSNN- site

Potentiometric and spectroscopic studies on the copper(II) complexes of rat amylin fragments. The anchoring ability of specific non-coordinating side chains

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Nickel(II), zinc(II) and cadmium(II) complexes of hexapeptides containing separate histidyl and cysteinyl binding sites

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Az átmenetifémionok peptidekkel alkotott komplexei. A fémion-fehérje kölcsönhatás modellezése. = Transition metal complexes of peptides. Models of the metal ion protein interactions.

1. Multihisztidin peptidek réz(II)- és cink(II)komplexei: A hisztidin nitrogén donoratomok a peptidek elsődleges fémkötőhelyei. Ezek koordinációjával makrokelátok képződhetnek, amelyek stabilitása a hisztidinek számától és távolságától függ. A karboxilcsoportok jelenléte a cink(II)komplexek stabilitását növeli. A réz(II)ionok az amidcsoport deprotonálódását is indukálhatják, ami többmagvú komplexek képződéséhez vezet. A megkötött rézionok száma megegyezik a hisztidinek számával. 2. A prion protein peptid fragmenseinek fémkomplexei: Az oktarepeaten kívüli hisztidinek is stabilis rézkötőhelyek. A HuPrP(84-114) fragmensre kapott eredmények szerint a kötési helyek stabilitási sora: His111 > His96 >> His85. Egyéb átmenetifémek komplexeit is tanulmányoztuk, amelyek stabilitási sora a következő: Pd(II) > Cu(II) > Ni(II) > Zn(II) > Cd(II) ~ Co(II) > Mn(II). 3. Az amyloid-? peptid réz(II)komplexei: Az A?(1-16) peptidnek kiugróan nagy rézionaffinitása van. A terminális aminocsoport az elsődleges fémkötőhely, amit a hisztidinek koordinációja követ. Egy A?(1-16) molekula 4 réziont képes megkötni. Az egy- két- és három-magvú komplexeknek koordinációs izomerjei lehetnek, de a terminális aminocsoport és a szomszédos amidnitrogének koordinációja preferált. | 1. Copper(II) and zinc(II) complexes of multihistidine peptides: Histidyl residues are the primary metal binding sites resulting in the formation of macrochelates. The stabilities of macrochelates are influenced by the number and location of histidyl residues. The stability of zinc(II) complexes is enhanced by the presence of carboxylate functions. Formation of polynuclear complexes has also been detected and their nuclearities correspond to the number of histidyl sites. 2. Metal binding affinity of prion peptide fragments: Histidyl residues outside the octarerepat domain are effective copper binding sites. The results obtained for the copper(II) complexes of HuPrP(84-114) revealed the following stability order: His111 > His96 >> His85. Complex formation with several other transition elements has also been studied and their stability order: Pd(II) > Cu(II) > Ni(II) > Zn(II) > Cd(II) ~ Co(II) > Mn(II). 3. Copper(II) complexes of amyloid-? peptide fragments: A?(1-16) has an outstanding affinity towards the complexation with copper. The terminal amino group is the primary metal binding site, followed by the coordination of histidyl residues. One molecule of A?(1-16) can bind as much as four copper(II) ions. Various coordination isomers of the mono-, di- and tri-nuclear complexes can exist with a preference for the coordination via the terminal amino and subsequent amide groups