Coordination pattern and reactivity of two model peptides from porin protein P1.

It has been reported that numerous of Fusobacterium nucleatum outer membrane proteins take part in cancerogenesis. Therefore, it is very interesting to study their interactions with metal ions and the ability to produce reactive oxygen species, which may be involved in cancer progression. Since investigations of metal binding to proteins are often based on fragments that contain the metal-binding domains, designing model peptides should be very mindful.

Protocol of proceedings with and optimization of ABTS method for detection of reactive oxygen species.

Characterization of the ability of DSM 15643 and DSM 20482 strains in the presence of Cu and HO to reactive oxygen species generation. Spectrophotometric ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) method was used. Determination of: MIC for Cu, HO and ABTS; survivability of under atmospheric oxygen exposure; the level and rate constants of free radicals production by the bacteria.

Phleomycin complex - Coordination mode and in vitro cleavage of DNA.

Phleomycin is one of the anticancer glycopeptide antibiotics which cause DNA cleavage. It is commonly used as a copper(II) complex. Therefore, it is important to study the metal ion binding process and to define the coordination mode.

Copper(II) complexes with Fusobacterium nucleatum adhesin FadA: Coordination pattern, physicochemical properties and reactivity.

Fusobacterium nucleatum is an anaerobic, Gram-negative bacteria linked to colon cancer. It is interesting to determine how metal ions interact with bacterial adhesin proteins. To this end, the coordination of ATDAAS-NH and MKKFL-NH fragments of Fusobacterium adhesin A (FadA) to copper(II) ions was studied by potentiometry, spectroscopic techniques (UV-Vis, CD, EPR and NMR) and the density functional theory (DFT) methods.

Cu and Cu complexes with phosphine derivatives of fluoroquinolone antibiotics - A comparative study on the cytotoxic mode of action.

In this paper, we present a comparative study on the cytotoxic mode of action of copper(I) and copper(II) complexes with phosphine derivatives of fluoroquinolone antibiotics (ciprofloxacin HCp and norfloxacin HNr). The in vitro cytotoxic activity of four new compounds was tested against two selected cancer cell lines. All complexes exhibited much better cytotoxicity against both cell lines than unmodified fluoroquinolone antibiotics, their phosphines (PCp, PNr), chalcogenide derivatives (oxides: OPCp, OPNr; sulfides: SPCp, SPNr and selenides: SePCp, SePNr) and previously described by us complexes with phosphines derived from different fluoroquinolones: lomefloxacin (HLm) and sparfloxacin (HSf) as well as cisplatin.

Peptides having antimicrobial activity and their complexes with transition metal ions.

Peptide antibiotics are produced by bacterial, mammalian, insect or plant organisms in defense against invasive microbial pathogens. Therefore, they are gaining importance as anti-infective agents. There are a number of antibiotics that require metal ions to function properly.

Impact of the Cu(II) ions on the chemical and biological properties of goserelin - coordination pattern, DNA degradation, oxidative reactivity and in vitro cytotoxicity.

Goserelin acetate (Gos) as a synthetic analog of the mammalian gonadotropin-releasing hormone (GnRH) is widely used in the treatment of sex hormone-related conditions. In this paper we present the chemical and biological aspects of its interaction with Cu(II) ions. The mode of Cu(II) binding and the thermodynamic stability of the obtained complexes were characterized by potentiometry, UV-Vis and CD spectroscopic methods.

Characterization of Highly Efficient RNA-Cleaving DNAzymes that Function at Acidic pH with No Divalent Metal-Ion Cofactors.

Here, we describe the characterization of new RNA-cleaving DNAzymes that showed the highest catalytic efficiency at pH 4.0 to 4.5, and were completely inactive at pH values higher than 5.

New copper(I) complexes bearing lomefloxacin motif: Spectroscopic properties, in vitro cytotoxicity and interactions with DNA and human serum albumin.

In this paper we present lomefloxacin's (HLm, 2nd generation fluoroquinolone antibiotic agent) organic and inorganic derivatives: aminomethyl(diphenyl)phosphine (PLm), its oxide as well as new copper(I) iodide or copper(I) thiocyanate complexes with PLm and 2,9-dimethyl-1,10-phenanthroline (dmp) or 2,2'-biquinoline (bq) as the auxiliary ligands. The synthesized compounds were fully characterised by NMR, UV-Vis and luminescence spectroscopies. Selected structures were analysed by theoretical DFT (density functional theory) methods.

New ruthenium(II) coordination compounds possessing bidentate aminomethylphosphane ligands: synthesis, characterization and preliminary biological study in vitro.

Addition of aminomethylphosphane P{CH2N(CH2CH2)2O}3 (), PPh2{CH2N(CH2CH2)2O} () or PPh2{CH2N(CH2CH2)2NCH2CH3} () to a methanolic solution of RuCl3 results in reduction of ruthenium(iii) ions giving finally ttt-[RuCl2()2] (), ttt-[RuCl2()2] () and ttt-[RuCl2()2] (). The synthesized complexes are the first examples of ruthenium(ii) coordination compounds possessing aminomethylphosphanes chelating via phosphorus and nitrogen atoms. They were fully characterized (NMR, ESI-MS, IR, elemental analysis, X-ray crystallography).

Copper(i) complexes with phosphine derived from sparfloxacin. Part I - structures, spectroscopic properties and cytotoxicity.

In this paper we present new copper(i) iodide or copper(i) thiocyanate complexes with hydroxymethyldiphenylphosphine (PPh2(CH2OH)) or phosphine derivatives of sparfloxacin, a 3(rd) generation fluoroquinolone antibiotic agent (PPh2(CH2-Sf)) and 2,9-dimethyl-1,10-phenanthroline (dmp) or 2,2'-biquinoline (bq) auxiliary ligands. The synthesised complexes were fully characterised by NMR and UV-Vis spectroscopy as well as by mass spectrometry. Selected structures were additionally analysed using X-ray and DFT methods.

Impact of Cu(2+) ions on the structure of colistin and cell-free system nucleic acid degradation.

Colistin and transition metal ions are commonly used as feed additives for livestock animals. This work presents the results of an analysis of combined potentiometric and spectroscopic (UV-vis, EPR, CD, NMR) data which lead to conclude that colistin is able to effectively chelate copper(II) ions. In cell-free system the oxidative activity of the complex manifests itself in the plasmid DNA destruction with simultaneous generation of reactive OH species, when accompanied by hydrogen peroxide or ascorbic acid.

Activity of fluconazole and its Cu(II) complex towards species.

species, although they are present as commensal organisms in the digestive tract of healthy individuals, can produce a broad spectrum of serious illnesses in compromised hosts. Fluconazole, a water-soluble triazole with bioavailability greater than 90 %, has been extensively used to treat a wide range of infections. However, a growing resistance of microorganisms in the treatment leads to the discovery of new drugs or modifications of existing ones.

In vitro selection of deoxyribozymes active with Cd(2+) ions resulting in variants of DNAzyme 8-17.

In vitro selection was performed to search for RNA-cleaving DNAzymes catalytically active with Cd(2+) ions from the oligonucleotide combinatorial library with a 23-nucleotide random region. All the selected, catalytically active variants turned out to belong to the 8-17 type DNAzyme. Three DNAzymes were prepared in shortened, cis-acting versions which were subjected to a detailed study of the kinetic properties and metal ion preferences.

Interaction of methotrexate, an anticancer agent, with copper(II) ions: coordination pattern, DNA-cleaving properties and cytotoxic studies.

The acid-base properties and the Cu(II) binding processes of methotrexate (MTX) were characterized by selected spectroscopic techniques and potentiometric measurements. The pH titration data showed that MTX behaves as a triprotic ligand. The deprotonation constants were determined for α-COOH and γ-COOH groups and (N1)H from the pteridine ring.

Acid-base characterization, coordination properties towards copper(II) ions and DNA interaction studies of ribavirin, an antiviral drug.

We have studied processes of copper(II) ion binding by ribavirin, an antiviral agent used in treating hepatitis C, which is accompanied usually by an increased copper level in the serum and liver tissue. Protonation equilibria and Cu(II) binding were investigated using the UV-visible, EPR and NMR spectroscopic techniques as well as the DFT (density functional theory) calculations. The spectroscopic data suggest that the first complex is formed in the water solution at pH as low as 0.

Antibiotic bacitracin induces hydrolytic degradation of nucleic acids.

Background: Bacitracin is a polypeptide antibiotic active against Gram-positive bacterial strains. Its mechanism of action postulates disturbing the cell wall synthesis by inhibiting dephosphorylation of the lipid carrier. We have discovered that bacitracin induces degradation of nucleic acids, being particularly active against RNA.

Revised coordination model and stability constants of Cu(II) complexes of tris buffer.

2-Amino-2-hydroxymethyl-propane-1,3-diol, or tris(hydroxymethyl)aminomethane (Tris), is probably the most common biochemical buffer used alone or in combination with other buffers because it is stable, unreactive, and compatible with most proteins and other biomolecules. Being nontoxic, it has even found applications in medicine. Tris is known, however, to coordinate transition metal ions, Cu(II) among them.

A rice fungicide blasticidin S efficiently binds Cu(II) ions and prevents DNA from metal-induced damage.

Blasticidin S is a representative of the aminoacylnucleoside class of antibiotics and it possesses fungicidal properties against the virulent fungus which causes a serious rice blast disease in Asia. It is widely used to control rice blast by foliar application as a crop protection agent. Serious copper contamination is observed in some areas of China.

Copper(I) (pseudo)halide complexes with neocuproine and aminomethylphosphines derived from morpholine and thiomorpholine - in vitro cytotoxic and antimicrobial activity and the interactions with DNA and serum albumins.

Herein, a series of CuI or CuNCS complexes with neocuproine (2,9-dimethyl-1,10-phenanthroline: dmp) and two tris(aminomethyl)phosphines derived from morpholine (P(CH2 N(CH2 CH2 )2 O)3 ) or thiomorpholine (P(CH2 N(CH2 CH2 )2 S)3 ) were tested as cytotoxic agents in vitro towards mouse colon carcinoma (CT26) and human lung adenocarcinoma (A549). The studies showed that the complexes exhibit potential antitumor properties, displayed by IC50 values below 10 μm towards the tested cell lines, in the case of 4-h incubation time with the examined compounds. Moreover, a high antimicrobial activity of all the complexes was observed against Staphylococcus aureus and Candida albicans with minimal inhibitory concentrations equal to 1-2 μg/mL.

High affinity of copper(II) towards amoxicillin, apramycin and ristomycin. Effect of these complexes on the catalytic activity of HDV ribozyme.

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.

Mapping the interactions of selected antibiotics and their Cu2+ complexes with the antigenomic δ ribozyme.

The interactions of selected antibiotics with the trans-acting antigenomic delta ribozyme were mapped. Ribozyme with two oligonucleotide substrates was used, one uncleavable with deoxycytidine at the cleavage site, mimicking the initial state of ribozyme, and the other with an all-RNA substrate mimicking, after cleavage, the product state. Mapping was performed with a set of RNA structural probing methods: Pb(2+) -induced cleavage, nuclease digestion, and the selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) approach.

Selective control of Cu(II) complex stability in histidine peptides by β-alanine.

The cooperativity of formation of 5-membered and 6-membered chelate rings is the driving force for specificity and selectivity in Cu(II) peptidic complexes. α-Amino acids enable the formation of 5-membered rings, while a 6-membered ring is provided by the coordination of the His side chain imidazole. Introduction of β-alanine is another way of creating a 6-membered ring in the Cu(II) complex.

Capreomycin and hygromycin B modulate the catalytic activity of the delta ribozyme in a manner that depends on the protonation and complexation with Cu2+ ions of these antibiotics.

Catalytic RNA molecules (ribozymes) have often been used for the testing of interactions of antibiotics with ribonucleic acids. We showed that the impact of capreomycin and hygromycin B on delta ribozyme catalysis might change dramatically, from stimulation to inhibition, depending on conditions. In order to evaluate possible mechanisms of modulation of the ribozyme catalytic activity we used our earlier data on species distribution for protonated forms of capreomycin and hygromycin B and their complexes with Cu(2+) ions at different pH values.

The impact of isomers of hemiaminal-1,2,4-triazole conjugates differently substituted in the phenyl ring and their Cu2+ complexes on the catalytic activity of the antigenomic delta ribozyme.

The ability of four stable hemiaminals differently substituted in the phenyl ring and their complexes with Cu(2+) ions to inhibit catalytic cleavage of the antigenomic delta ribozyme was compared. The hemiaminals were novel chiral derivatives of 1,2,4-triazole [i.e.