Gianni Valensin

Wyższa Szkoła Handlowa we Wrocławiu, Vrotslav, Lower Silesian Voivodeship, Poland

Are you Gianni Valensin?

Claim your profile

Publications (184)477.48 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Three representatives of the distinct antibiotics groups: amoxicillin, apramycin and ristomycin A were studied regarding their impact on hepatitis D virus (HDV) ribozyme both in the metal-free form and complexed with copper(II) ions. Hence the Cu(II)-ristomycin A complex has been characterized by means of NMR, EPR, CD and UV-visible spectroscopic techniques and its binding pattern has been compared with the coordination modes estimated previously for Cu(II)-amoxicillin and Cu(II)-apramycin complexes. It has thus been found that all three antibiotics bind the Cu(II) ion in a very similar manner, engaging two nitrogen and two oxygen donors into coordination with the square planar symmetry in physiological conditions. All three tested antibiotics were able to inhibit the HDV ribozyme catalysis. However, in the presence of the complexes, the catalytic reactions were almost completely inhibited. It was important therefore to check whether the complexes used in lower concentrations could inhibit the HDV ribozyme catalytic activity, thus creating opportunities for their practical application. It turned out that the complexes used in the concentrations of 50μM influenced the catalysis much less effectively comparing to the 200 micromolar concentration. The kobs values were lower than those observed in the control reaction, in the absence of potential inhibitors: 2-fold for amoxicillin, ristomycin A and 3.3-fold for apramycin, respectively.
    Journal of inorganic biochemistry 03/2013; 124C:26-34. · 3.25 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Des-acyl-ghrelin is a 28 amino acid peptide secreted by both human and rat stomach. Together with ghrelin and obestatin, it is obtained by post-translational modification of a 117 aminoacid prepropeptide mainly expressed in distinct endocrine cell type in the stomach. Although its receptor has not been unambiguously identified so far, des-acyl-ghrelin is considered one of the strongest antagonists of ghrelin in activating the growth hormone secretagogue receptor (GHS-R). Here the secondary structure of des-acyl-ghrelin in different experimental conditions has been investigated and compared with that of obestatin, a bioactive peptide having similar biological functions. CD and NMR techniques have been combined for gaining the desired conformational features. The obtained structures support a steady alpha-helix structure spanning residues from 7 to 14, very similar to that observed for obestatin at the same experimental conditions, leading to suggest that a similar secondary structure can be associated with the similar biological role.
    Peptides 03/2013; · 2.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aggregation of α-synuclein (αS) is a critical step in the etiology of Parkinson's disease. Metal ions such as copper and iron have been shown to bind αS, enhancing its fibrillation rate in vitro. αS is also susceptible to copper-catalyzed oxidation that involves the reduction of Cu(II) to Cu(I) and the conversion of O(2) into reactive oxygen species. The mechanism of the reaction is highly selective and site-specific and involves interactions of the protein with both oxidation states of the copper ion. The reaction can induce oxidative modification of the protein, which generally leads to extensive protein oligomerization and precipitation. Cu(II) binding to αS has been extensively characterized, indicating the N terminus and His-50 as binding donor residues. In this study, we have investigated αS-Cu(I) interaction by means of NMR and circular dichroism analysis on the full-length protein (αS(1-140)) and on two, designed ad hoc, model peptides: αS(1-15) and αS(113-130). In order to identify and characterize the metal binding environment in full-length αS, in addition to Cu(I), we have also used Ag(I) as a probe for Cu(I) binding. Two distinct Cu(I)/Ag(I) binding domains with comparable affinities have been identified. The structural rearrangements induced by the metal ions and the metal coordination spheres of both sites have been extensively characterized.
    Inorganic Chemistry 01/2013; · 4.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The binding mode provided by an unprotected peptide with non-coordinating side-chains is simple and well understood. However, when particular residues are inserted into the peptide sequence, they can have a significant impact on the stability of the formed complexes. The presence of non-bonding side chains of amino acids close to the metal binding centre in the peptide/protein can provide special interactions which result in increasing the stabilization of the formed species. Moreover, these interactions can play a crucial role in generating particular protein structures and in influencing biological activity. In the present paper it is shown how peptides with no specific predisposition for metal binding, like ANF peptides, can form metal complexes with a very high thermodynamic stability. For better understanding this peculiar behavior, a combined pH-metric and spectroscopic method was used to determine the stability and the solution structure of Cu(2+) and Ni(2+) complexes with NSFRY-NH(2) (ANF peptide) and a series of analogue peptides. All obtained data support the hypothesis that the complex-formation process is very similar for both metal ions and all the ligands, involving some intramolecular interactions among the different side chains. The two-dimensional NMR analysis of nickel complexes showed the occurrence of many inter-residue correlations and suggested the presence of a direct interaction between the d electrons of the metal ion and the π-ring system of the aromatic side-chains of the ligand.
    Dalton Transactions 10/2012; · 3.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer's disease (AD) is the leading cause of senile dementia. One of the main hallmarks of AD is the presence of amyloid plaques in the brain, primarily formed by fibrils of the amyloid-β (Aβ) peptide. Transition metal ions, such as Cu(2+) and Zn(2+) have been found at high concentrations in senile plaques isolated from AD patients and evidence have been reached that (i) Aβ aggregation is greatly affected by Cu(2+) and Zn(2+) and (ii) Cu(2+), implicated in the formation of reactive oxygen species, leads to mitochondrial dysfunctions ultimately leading to neuronal cells death. Aβ, apart from being toxic to neural cells, induces reactive astrocytosis in cell culture. Astrocytes play many crucial roles to sustain normal brain function by maintaining the cerebral homeostasis, modulating the synaptic transmission, and providing a metabolic support for neuronal growth. Although many studies have shown that Aβ fibrils interfere in the main astrocytic functions aimed at supporting the neuronal activity, nothing is known about the effects of Zn(2+)- and Cu(2+)-induced Aβ aggregates on astrocyte functions. In this study the effects of treatments with Aβ(42), either in absence or in the presence of Cu(2+) and Zn(2+), on astrocyte cell cultures were evaluated by using classical cellular assay and by looking at changes in metabolic profiles in the cellular medium by using nuclear magnetic resonance spectroscopy (NMR). Our results indicate that metal induced Aβ aggregation strongly affects the metabolites involved in the neurotransmission activity supporting a deleterious impact of Cu(2+) and Zn(2+) Aβ amyloidogenesis on astrocyte functions.
    Journal of inorganic biochemistry 09/2012; · 3.25 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cysteine and histidine residues are tempting donors for Ni2+ which coordinates to the sulfur of Cys and amide nitrogen atoms, or, in the absence of available thiol groups, to His imidazoles and amides. Bi3+, on the other hand, has a very strong affinity towards Cys thiol groups, and can also coordinate an additional His imidazole.In this review, the complicated pathway of nickel uptake, delivery and regulation in microorganisms is summarized. We show potential binding sites, binding geometries, protein structures and discuss the predicted thermodynamic and kinetic aspects. We focus on the numerous recent observations on the homeostasis of nickel in Helicobacter pylori (H. pylori), a Gram-negative bacterium that colonizes the gastric mucosa in humans, and is the causative agent of acute and chronic gastritis, peptic ulcer disease, gastric carcinoma, and gastric lymphoma.The homeostasis of Ni2+ is crucial for the survival of H. pylori in the extremely acidic environment of the stomach. The metal is delivered to urease (which catalyzes the hydrolysis of urea into carbon dioxide and ammonia and therefore neutralizes the low gastric pH) and to hydrogenase (which permits respiratory based energy production for the bacteria in the mucosa) by a set of accessory proteins. Most of the bacterium's metal metabolism is centered upon their expression and maturation.Below, a detailed description of the structural and thermodynamic aspects of the binding of nickel ions to poly-histidyl and poly-cysteil sites of urease and hydrogenase accessory proteins is given. Because bismuth compounds are one of the treatments for peptic ulcer disease, the inhibitory effect of Bi3+ ions is described; the affinity of bismuth towards Cys side groups is much stronger than the affinity of nickel towards the same sites, therefore bismuth is able to displace nickel from its binding site, causing the inhibition of nickel chaperones.
    Coordination Chemistry Reviews 01/2012; 256:133-148. · 11.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Capreomycin is an important therapeutic agent having intriguing and diverse molecular features. Its polypeptidic structure rich in nitrogen donors makes the drug a promising chelating agent for a number of transition metal ions, especially for copper(II). The results of the model investigational studies suggest that capreomycin anchors Cu(2+) ion with an amino function of the α,β-diaminopropionic acid residue at pH around 5. At physiological pH copper(II) ion is coordinated by two deprotonated amide nitrogen atoms of the α,β-diaminopropionic acid, the serine residue as well as the amino function deriving from the β-lysine. Above that pH value we observe a rearrangement within the coordination sphere leading to movement of Cu(2+) to the center of the peptide ring with concurrent coordination of four nitrogen donors. Spin-lattice relaxation enhancements and potentiometric measurements clearly indicate that deprotonated amide nitrogen atom from the β-ureidodehydroalanine moiety is the fourth donor atom.
    Journal of inorganic biochemistry 09/2011; 106(1):111-6. · 3.25 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The reactions of human β-amyloid peptide 1-28 (Aβ28) with Al(III) and Fe(III) ions were investigated by (1)H NMR and electrospray ionization mass spectrometry (ESI-MS) under pH conditions close to physiological ones. (1)H NMR titrations, performed in the 5.3-8.0 pH range, revealed that no measurable amounts of Aβ28-Al(III) or Aβ28-Fe(III) adducts are formed; such metal adducts could not be obtained even by changing a number of experimental conditions, e.g., temperature, buffer, nature of the salt, etc. These observations were later confirmed by ESI-MS. It is thus demonstrated that Aβ28, at physiological pH, is not able to form binary complexes with Al(III) and Fe(III) ions of sufficient stability to compete with metal hydroxide precipitation. The biological implications of these findings are discussed in the frame of current literature.
    Inorganic Chemistry 06/2011; 50(15):6865-7. · 4.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The relative conformation of the aromatic rings and the amide bridge as well as important details of the two side chains of the title compound in a DMSO-d6 solution have been established by use of non-selective and selective proton spin-lattice relaxation times coupled with nOe experiments. The complete analysis of 13C spin-lattice relaxation times has shown the main features of the dynamic behavior of the title compound.
    Canadian Journal of Chemistry 02/2011; 62(11):2131-2135. · 0.96 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Dynamic features were investigated in a homologous series of synthesized drugs having pharmacologic activity, with particular emphasis on relative motions of the two side chains anchored to a backbone of two aromatic rings linked by an amide bridge. A general and deep insight was reached by using a model-free approach. Conformational and motional dynamics within the compound exhibiting maximum activity were delineated and the most relevant parameters for pharmacologic action were defined.
    Canadian Journal of Chemistry 02/2011; 64(10):2048-2052. · 0.96 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Dynamic and geometric features of pilocarpine in water solution were delineated by interpreting 13C and 1H NMR spin-lattice relaxation rates and nuclear Overhauser effects. The motional correlation time was evaluated at 53 ± 5 ps at 298 K. 1H—1H distances, as calculated from double-selective 1H spin-lattice relaxation rates, and 13C—1H distances, as calculated from selective 13C–{1H} Overhauser effects, gave evidence of a C7 puckered conformation of the furanone ring and of an angle of ca. 50° between the two rings.
    Canadian Journal of Chemistry 02/2011; 71(5):738-741. · 0.96 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Copper interaction with alpha synuclein (αS) has been shown to accelerate aggregation and oligomerization of the protein. Three different αS copper binding domains have been proposed: (i) the N-terminal residues (1-9) that represent the minimal copper binding domain; (ii) the His-50 imidazole and (iii) the Asp and Glu residues within the acidic C-terminal domain. The copper coordination at the N-terminus has been extensively characterized and it is generally accepted that it provides the highest affinity site. The same does not hold for the role played by His-50 in copper binding. In this work Cu(ii) coordination to peptide fragments encompassing residues 45-55 of αS has been exhaustively characterized, including systems containing the inherited mutations E46K and A53T, as model peptides of the His-50 site. Through potentiometric titrations all the speciation profiles have been determined and the stability constants have been used to estimate the dissociation constants of complexes corresponding to the binding modes at pH 6.5 and 7.5. Spectroscopic analyses allowed determination of (i) the copper coordination sphere, (ii) its geometry and (iii) the constraints wherefrom the 3D structural models of the copper complexes could be obtained.
    Metallomics 01/2011; 3(3):292-302. · 4.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aminoglycosidic antibiotic hygromycin B presents a peculiar chemical structure, characterized by two sugar rings joined via a spiro connection. The Cu(ii) complex of hygromycin B in water solution was characterized by (1)H-NMR, UV-Vis, EPR and CD spectroscopy, combined with potentiometric measurements. The spin-lattice relaxation enhancements were interpreted by the Solomon-Bloembergen-Morgan theory, allowing us to calculate copper-proton distances that were used to build a model of the complex by molecular mechanics and dynamics calculations. The fidelity of the proposed molecular model was checked by ROESY maps. Moreover DNA damage by the Cu(ii)-hygromycin B system was also investigated, showing single and double strand scissions exerted by the complex at concentrations in the range 1-5 mM. Addition of either hydrogen peroxide or ascorbic acid to each sample resulted in the shift of the cleavage potency towards lower concentrations of the complex.
    Dalton Transactions 11/2010; 39(41):9830-7. · 3.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Zinc binding to P113 (or demegen), a 12 amino acid (AKRHHGYKRKFH-NH(2)) fragment of histatin 5, was investigated by means of NMR and CD techniques, yielding delineation of the metal binding site and the 3D structure of the complex in water and in DMSO as well. The three His imidazole and the N-terminus nitrogens were found to act as the zinc coordinating atoms. A comparison with the previously reported Cu(II)-P113 complex disclosed that the two structures were rather diverse, in spite of an identical donor set. The two complexes were also tested for their antimicrobial activity in vitro against seven bacteria and two yeast strains: a minor activity of both complexes vs that of free ligand was given evidence, suggesting both metal ions may possibly play a negative role in vivo.
    Inorganic Chemistry 10/2010; 49(19):8690-8. · 4.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aggregation of alpha-synuclein (AS) is a critical step in the etiology of Parkinson's disease (PD). A central, unresolved question in the pathophysiology of PD relates to the role of AS-metal interactions in amyloid fibril formation and neurodegeneration. Our previous works established a hierarchy in alpha-synuclein-metal ion interactions, where Cu(II) binds specifically to the protein and triggers its aggregation under conditions that might be relevant for the development of PD. Two independent, non-interacting copper-binding sites were identified at the N-terminal region of AS, with significant difference in their affinities for the metal ion. In this work we have solved unknown details related to the structural binding specificity and aggregation enhancement mediated by Cu(II). The high-resolution structural characterization of the highest affinity N-terminus AS-Cu(II) complex is reported here. Through the measurement of AS aggregation kinetics we proved conclusively that the copper-enhanced AS amyloid formation is a direct consequence of the formation of the AS-Cu(II) complex at the highest affinity binding site. The kinetic behavior was not influenced by the His residue at position 50, arguing against an active role for this residue in the structural and biological events involved in the mechanism of copper-mediated AS aggregation. These new findings are central to elucidate the mechanism through which the metal ion participates in the fibrillization of AS and represent relevant progress in the understanding of the bioinorganic chemistry of PD.
    Inorganic Chemistry 10/2010; 49(22):10668-79. · 4.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The reaction of the ruthenium(II) complex fac-[Ru(CO)(3)Cl(2)(N(1)-thz)] (I hereafter; thz = 1,3-thiazole) with human beta-amyloid peptide 1-28 (Abeta(28)) and the resulting {Ru(CO)(3)}(2+) peptide adduct was investigated by a variety of biophysical methods. (1)H NMR titrations highlighted a selective interaction of {Ru(CO)(3)}(2+) with Abeta(28) histidine residues; circular dichroism revealed the occurrence of a substantial conformational rearrangement of Abeta(28); electrospray ionization mass spectrometry (ESI-MS) suggested a prevalent 1:1 metal/peptide stoichiometry and disclosed the nature of peptide-bound metallic fragments. Notably, very similar ESI-MS results were obtained when I was reacted with Abeta(42). The implications of the above findings for a possible use of ruthenium compounds in Alzheimer's disease are discussed.
    Inorganic Chemistry 06/2010; 49(11):4720-2. · 4.59 Impact Factor
  • ChemBioChem 12/2009; 11(2):166-9. · 3.74 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Teicoplanin, a member of the "last chance" antibiotic family has a similar structure and the same mechanism of action as parent drug vancomycin, which is proved to be an effective binder of Cu(II) ions. However, the potentiometric and spectroscopic studies (UV-visible, CD, NMR) have shown that the modification of the N-terminal structure of the peptide backbone in teicoplanin affects considerably the binding ability towards Cu(II) ions. While vancomycin forms almost instantly the stable 3N complex species involving the N-terminal and two amide nitrogen donors, in case of teicoplanin only two nitrogen donors derived from the N-terminal amino group and adjacent peptide bond are coordinated to Cu(II) ion within the whole pH range studied. The major factor influencing the binding mode is most likely the structure of the N-terminus of the peptide unit in the antibiotic ligand.
    Journal of inorganic biochemistry 11/2009; 104(2):193-8. · 3.25 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Both human (h) and chicken (Ch) prion proteins (PrP) bind copper ions within the so called "tandem repeat" N-terminal region. Outside this region, hPrP possesses two additional copper binding sites, localized at His-96 and His-111 in the so called "amylodogenic" or neurotoxic region (residues 91-126). Also ChPrP possesses a similar region (ChPrP(105-140)) containing two His (His-110 and His-124) and an identical hydrophobic tail of 15 amino acids rich in Ala and Gly. The copper binding abilities within such region of ChPrP were investigated by NMR, CD and potentiometry using Ni(2+) as diamagnetic probe. The formation of diamagnetic metal complexes allowed to monitor the chemical shift and signal intensity variations and to determine the structural and kinetic features of the His-110 and His-124 metal binding sites. Finally a comparison between the hPrP and ChPrP metal binding abilities was performed. We found that the two prion proteins exhibited different copper and nickel preferences with the favoured metal binding sites localized at opposite His: His-110 for ChPrP, and His-111 for hPrP.
    Journal of inorganic biochemistry 10/2009; 104(1):71-8. · 3.25 Impact Factor
  • Inorganic Chemistry 09/2009; · 4.59 Impact Factor

Publication Stats

940 Citations
477.48 Total Impact Points

Institutions

  • 2005–2013
    • Wyższa Szkoła Handlowa we Wrocławiu
      Vrotslav, Lower Silesian Voivodeship, Poland
  • 1975–2013
    • Università degli Studi di Siena
      • Department of Medicine, Surgery and Neuroscience
      Siena, Tuscany, Italy
  • 2012
    • Wroclaw Medical University
      • Department of Inorganic Chemistry
      Wrocław, Lower Silesian Voivodeship, Poland
  • 2005–2009
    • University of Wroclaw
      • Faculty of Chemistry
      Wrocław, Lower Silesian Voivodeship, Poland
  • 2007
    • University of Silesia in Katowice
      • Faculty of Mathematics, Physics and Chemistry
      Katowice, Silesian Voivodeship, Poland
  • 2006
    • University of Zurich
      Zürich, Zurich, Switzerland
  • 1989–2005
    • Università degli Studi della Basilicata
      Potenza, Basilicate, Italy
  • 2004
    • Universita degli studi di Ferrara
      • Department of Chemical and Pharmaceutical Sciences
      Ferrara, Emilia-Romagna, Italy
  • 2002
    • Università degli Studi di Torino
      Torino, Piedmont, Italy
  • 1998–2000
    • Sapienza University of Rome
      • Department of Chemistry
      Roma, Latium, Italy
  • 1982
    • Tel Aviv University
      • Department of Chemistry
      Tell Afif, Tel Aviv, Israel