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At least 289 records · Page 16Linked to original sources
PubMed2006

Chromatographic enantioseparation of amino acids using a new chiral stationary phase based on a macrocyclic glycopeptide antibiotic.

The separation of the enantiomers of several a-amino acids was studied on a new chiral stationary phase (CSP) which is based on the macrocyclic glycopeptide antibiotic eremomycin attached to silica particles. Retention and separation factors were determined under analytical conditions at ambient temperature for different mobile phase compositions. In order to evaluate the potential with respect to preparative separations the adsorption isotherms of D- and L-methionine were determined for one mobile phase composition applying the elution by characteristic point method. The isotherms were validated by comparing experimentally determined elution profiles with predictions based on the equilibrium dispersive model. Finally, the performance of the eremomycin CSP was compared with a commercially available CSP based on the macrocyclic antibiotic teicoplanin. After determining the isotherms of D- and L-methionine also for the teicoplanin phase, the equilibrium dispersive model was used for both CSP to identify optimal operating conditions. For the separation and conditions considered the new eremomycin CSP revealed a better performance compared to the teicoplanin CSP.

Adsorption↗
PubMed2002

MR angiography with a new rapid-clearance blood pool agent: Initial experience in rabbits.

The purpose of this study was to assess a new Gd-based macromolecular intravascular contrast agent (P792, Vistarem(R); Laboratoire Guerbet, Aulnay sous Bois, France) for MR angiography (MRA). P792 is a macrocyclic gadolinium compound based on a gadoterate meglumine structure substituted by hydrophilic arms. In vitro imaging of phantoms containing varying concentrations of P792 and gadoterate meglumine (Gd-DOTA) was performed. In rabbits (N = 5), arterial concentrations for P792 and Gd-DOTA were determined, and in vivo 3D MRA was performed. For gadolinium concentrations ranging from 200 to 3000 micromol/l, in vitro imaging showed higher SNR values for P792 compared to Gd-DOTA. Determination of arterial Gd concentration showed comparable bolus phase curves for P792 and Gd-DOTA. With P792, higher concentrations were obtained due to a restricted diffusion into the interstitial space. P792 allowed acquisition of high-quality MR angiograms. Image quality was rated as superior for P792 in the post-bolus phase images. In conclusion, P792 appears to be well suited for high-quality first-pass and equilibrium-phase MRA. The intravascular properties lead to an excellent signal in the vasculature, with limited background enhancement. Since the agent is rapidly renally excreted, it should be well suited for perfusion and permeability imaging.

Animals↗
PubMed2001

Inhibition of CaT1 channel activity by a noncompetitive IP3 antagonist.

A newly cloned, human epithelial Ca2+ transport protein (CaT1) was expressed in Xenopus laevis oocytes, and its single channel characteristics were examined. The CaT1 channel shows a strong dependence upon hyperpolarizing voltages, being activated by very negative voltages. The probability of channel opening and mean open times increase substantially at more negative voltages in the range of -90 to -160 mV. In addition, CaT1 channel activity was markedly inhibited by micromolar levels of a noncompetitive antagonist of the IP3 receptor originally isolated from a marine sponge, Xestospongin C. This inhibitory effect could be mediated indirectly via the binding of Xestospongin C to the inositol-trisphosphate (IP3) receptor or, alternatively, by a direct action on the CaT1 channel itself. Independent of its mechanism of action in inhibiting CaT1, Xestospongin C will provide a useful tool for elucidating the physiological role(s) of this novel epithelial Ca2+ channel.

Animals↗
PubMed2002

Phospholipase D regulates calcium oscillation frequency and nuclear factor-kappaB activity in histamine- stimulated human endothelial cells.

Histamine stimulates [Ca(2+)](i) oscillations in human aortic endothelial cells (HAEC), the frequency of which regulates the activity of nuclear factor-kappaB (NF-kappaB). This study was performed to determine whether phospholipase D (PLD) is involved in this signaling pathway. At a concentration of 1 microM, which stimulates [Ca(2+)](i) oscillations in this cell type, histamine initiated a twofold increase in [(32)P]phosphatidybutanol (PBt), an index of PLD activity as early as 5 min after stimulation. During established [Ca(2+)](i) oscillations induced by 1 microM histamine, 0.3% n-butanol, which "functionally" redirects phosphatidic acid formed by PLD to PBt, decreased [Ca(2+)](i) oscillation frequency by approximately 50% and produced a similar reduction in NF-kappaB activity. In the presence of the inositol 1,4,5-trisphosphate receptor blocker xestospongin C, which itself decreases the frequency of histamine-stimulated [Ca(2+)](i) oscillations, n-butanol produced a further decrease in oscillation frequency that was not associated with an additional reduction in NF-kappaB activity. This study shows that activation of PLD by histamine regulates [Ca(2+)](i) oscillation frequency and NF-kappaB activity in HAEC.

1-Butanol↗
PubMed1984

Nematospiroides dubius: response of the late fourth-stage larva to anthelmintics in vitro.

Approximately 60% of fourth-stage larvae of Nematospiroides dubius recovered from mice 6 days after infection, developed to the young adult stage when cultured over a 7-day period in a complex medium in vitro. Larvae at the late fourth stage of development were found to be highly susceptible to most broad spectrum anthelmintics under in vitro conditions, the benzimidazole, imidazothiazole, pyrimidine, isothiocyanate and macrocyclic lactone compounds all being active at very low concentrations. Narrow spectrum anthelmintics active only against ascarids, pinworms, filariae, cestodes or trematodes had little or no effect on these larvae. Ineffective also were those chlorinated hydrocarbon, substituted phenol and salicylanilide compounds known to affect Haemonchus but not trichostrongylid worms in general. It is concluded that in vitro assays employing larvae of N. dubius are useful for the stringent screening of compounds for broad spectrum antitrichostrongyle activity. Used in conjunction with in vivo screens employing N. dubius in mice, they also afford means for detecting intrinsic activity against the parasite in a system free from any complicating host pharmacokinetics.

Animals↗
PubMed2006

Cobalt(II)-selective membrane sensor based on a [Me2(13)dieneN4] macrocyclic cobalt complex.

A new poly(vinyl chloride)-based membrane was fabricated with the cobalt(II) complex of 2,4-dimethyl-1,5,8,11-tetraazacyclotrideca-1,4-diene [Me2(13)dieneN4] as an ion carrier. The membrane composition was Co2+ complex/PVC/NaTPB/DBP 15:50:15:20 (w/w). The sensor exhibited a Nernstian response for Co2+ ions over a wide concentration range (7.94x10(-6)-1.0x10(-1) M) at pH 2.5-7.0, a response time of 10 s, and it could be used for 3 months without any significant divergence in potential. The proposed membrane sensor exhibited good selectivity for Co2+ over a wide variety of other metal ions and in mixtures containing up to 25% (v/v) non-aqueous content. The sensor was successfully used as an indicator electrode in the potentiometric titration of Co2+ with EDTA and the direct determination of Co2+ in real samples.

Biosensing Techniques↗
PubMedDate not supplied

Platelet aggregation inhibitors from Philippine marine invertebrate samples screened in a new microplate assay.

A new microplate assay for Ca(2+)-induced platelet aggregation as detected by Giemsa dye was used to screen marine invertebrate samples from the Philippines for inhibitors of human platelet aggregation. Out of 261 crude methanol extracts of marine sponges and tunicates, 25 inhibited aggregation at 2 mg/ml. Inhibition of agonist-induced aggregation in an aggregometer was used to confirm results of the microplate assay and to determine the specific mode of inhibition of 2 samples. The marine sponge Xestospongia sp. yielded a xestospongin/araguspongine-type molecule that inhibited collagen-induced aggregation by 87% at 2 micro g/ml, and epinephrine-induced aggregation by 78% at 20 micro g/ml, while the marine sponge Aplysina sp. yielded 5,6-dibromotryptamine, which inhibited epinephrine-induced aggregation by 51% at 20 micro g/ml. In this study we have found that the microplate assay is a simple, inexpensive, yet useful preliminary tool to qualitatively screen a large number of marine samples for antiplatelet aggregation activity.

Adenosine Diphosphate↗
PubMed2005

New modulated metallic macrocycles: Electrochemistry and their interaction with calf thymus DNA.

New modulated pentacoordinate complexes [C17H34N7O2Cu]ClO4 (5), [C17H34N7O2Co]ClO4 (6), [C17H34N7O2Ni] ClO4 (7) have been synthesized by the interaction of 1,8-dihydro-1,3,6,8,10,13 Cu(II) (2), Co(II) (3), Ni(II) (4) hexaazacyclotetradecane complexes and Hsalea N-(2-hydroxy benzyl)-2-amino-1-ethanol ligand (1). All the complexes have been characterized by infrared, electron paramagnetic resonance, 1H and 13C nuclear magnetic resonance (NMR), 2D correlation spectroscopy NMR and ultraviolet-visible (UV-vis) spectroscopy. In all the complexes, the metal center is encapsulated by the Hsalea ligand in a pentacoordinate environment-vis absorption titration and viscometric studies have been carried out to ascertain the interaction of complexes 5 and 6 with calf thymus DNA (CT DNA). The experimental results suggest that complex 5 binds to CT DNA through partial intercalation of the aromatic ring into the base pair of DNA while complex 6 binds binds to CT DNA by electrostatic mode. The intrinsic binding constants K(b) of complex 5 and 6 were found to be 6.8 x 10(-5) M(-1) and 1.8 x 10(-4) M(-1), respectively. The binding of complexes 5 and 6 with CT DNA has also been investigated by cyclic voltammetry.

Biocompatible Materials↗
PubMed2004

Disorazol A1, a highly effective antimitotic agent acting on tubulin polymerization and inducing apoptosis in mammalian cells.

Disorazol A1, a macrocyclic polyketide compound that is produced by the myxobacterium Sorangium cellulosum showed a remarkably high cytostatic activity. It inhibited the proliferation of different cancer cell lines including a multidrug-resistant KB line at low picomolar levels. In presence of disorazol A1, the nuclei of the cells increased in size and the cells often became multinucleate. Low concentrations of disorazol (<100 pM) induced an apoptotic process, characterized by enhanced capase-3 activity and DNA laddering, and abnormal, multipolar mitotic spindles. Low concentrations also induced an accumulation of p53 protein in the nucleus. At higher concentrations, we observed an accumulation of the cells in the G2/M-phase of the cell cycle, and a depletion of microtubules. In vitro, disorazol A1 inhibited the polymerization of tubulin in a concentration-dependent manner and independently of microtubule-associated proteins. Correspondingly it induced a complete depolymerization of microtubules prepared in vitro. Formation of defined degradation structures was not observed. Disorazol is a novel, highly effective antimitotic agent. Efforts are going on to develop it as an anticancer drug.

Antineoplastic Agents↗
PubMed2006

Electrochemical detection of scDNA cleavage in the presence of macrocyclic hexaaza-copper(II) complex.

The hexaaza macrocyclic copper(II) complex Cu(II)L(L=1,8-Dihydroxyethyl-1,3,6,8,10,13-hexaazacyclotetradecane), which has octahedral structure similar to some natural complexes, is synthesized and purified. In this study, oxidative breakage DNA by the reaction of Cu(II)L with H2O2 and ascorbate has been investigated by gel electrophoresis experiments. In electrochemical experiments, the on scDNA-modified glassy carbon electrode(GCE) is cleaved by the Cu(II)L and redox changing of the metal catalyst without adding any other reagents. Above all, the need for concentration of scDNA is much lower than that of gel electrophoresis experiments and the process of the performance is easy. Furthermore, Cyclic Voltammetry (CV) and A.C. Impedance, which are performed to monitor scDNA cleavage at the scDNA-modified glassy carbon electrode (GCE), are fast, simple and highly efficient. The mechanism of the damage can be suggested: Fenton.

Ascorbic Acid↗
PubMed2005

Dinuclear macrocyclic polyamine zinc(II) complexes linked with flexible spacers: synthesis, characterization, and DNA cleavage.

Dinuclear macrocyclic polyamine zinc(II) complexes, which have two cyclen groups linked by flexible spacers, have been synthesized as DNA cleavage agents. The structures of these new dinuclear complexes are consistent with the data obtained from elemental analysis, MS and 1H NMR spectroscopy. The catalytic activity of these dinuclear complexes on DNA cleavage was studied. The results showed that the dinuclear zinc(II) complexes can catalyze the cleavage of supercoiled DNA (pUC 19 plasmid DNA) (Form I) under physiological conditions to produce selectively nicked DNA (Form II).

DNA↗
PubMed2005

1H NMR studies of homo and mixed ligand complexes of Tl+ ion with several polyazamacrocycles.

Proton NMR was used as a probe to study the interaction of the Tl(+) ion with 9-18-membered macromonocyclic tri-, tetra-, and hexaamines in dimethylformamide (DMF) solution. A study of proton chemical shift of ligands as a function of Tl(+) ion to ligand mole ratio revealed that the complexation reactions occur in a stepwise manner. Formation of a 1:1 complex is followed by the addition of a second complexant molecule to form a homo-sandwich complex for triazamacrocycle ligands and a mixed ligand complex in the case of hexamethylhexacyclen (HMHCY) and 1,4,7-triazacyclononane ([9]aneN(3)). The formation constants of resulting 1:1 and 1:2 (homo and mixed ligand sandwich) complexes in DMF solution were evaluated from computer fitting of the chemical shift-mole ratio data. The mixed ligand complexes may be more stable than the parent complex in which both ligands are the same. The influence of cavity size and substitution of methyl groups on nitrogen atoms of the macrocyclic ring the stability of the resulting complexes is discussed. The geometries of the tri- and tetraazamacrocycle ligands and their Tl(+) ion complexes were optimized by an ab initio method, and the calculated binding energies of resulting complexes were compared. Both the experimental and theoretical studies revealed that, in the presence of methyl groups, the stability of triazamacrocycle complexes with Tl(+) ion was decreased.

Dimethylformamide↗
PubMed2005

Evaluation of macrocyclic Grb2 SH2 domain-binding peptide mimetics prepared by ring-closing metathesis of C-terminal allylglycines with an N-terminal beta-vinyl-substituted phosphotyrosyl mimetic.

Preferential binding of ligands to Grb2 SH2 domains in beta-bend conformations has made peptide cyclization a logical means of effecting affinity enhancement. This is based on the concept that constraint of open-chain sequences to bend geometries may reduce entropy penalties of binding. The current study extends this approach by undertaking ring-closing metathesis (RCM) macrocyclization between i and i+3 residues through a process involving allylglycines and beta-vinyl-functionalized residues. Ring closure in this fashion results in minimal macrocyclic tetrapeptide mimetics. The predominant effects of such macrocyclization on Grb2 SH2 domain binding affinity were increases in rates of association (from 7- to 16-fold) relative to an open-chain congener, while decreases in dissociation rates were less pronounced (approximately 2-fold). The significant increases in association rates were consistent with pre-ordering of solution conformations to near those required for binding. Data from NMR experiments and molecular modeling simulations were used to interpret the binding results. An understanding of the conformational consequences of such i to i+3 ring closure may facilitate its application to other systems where bend geometries are desired.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Chiral multinuclear macrocyclic polyamine complexes: synthesis, characterization and their interaction with plasmid DNA.

A series of multinuclear macrocyclic polyamine metal (Zn(2+), Cu(2+), Co(2+)) complexes containing chiral dipeptide linkage were synthesized and used as artificial nuclease enzyme model. The interaction between the complexes and plasmid DNA (pUC19) was studied, and the results revealed that these complexes could act as powerful catalysts for the cleavage of plasmid DNA under physiological conditions.

Catalysis↗
PubMed2004

Macrocyclic proteoglycan mimics. Potent inhibition of cell adhesion by a bundle of chondroitin sulfate chains assembled on the calix[4]resorcarene platform.

Tailed calix[4]resorcarene macrocycle (tail=undecyl) can be used as a platform to assemble four glycosaminoglycan polysaccharide chains to give a new type of proteoglycan mimics. A tetra(chondroitin sulfate) derivative thus obtained from the reaction of macrocyclic octaamine and chondroitin sulfate lactone is readily immobilized on a tissue culture plastic (polystyrene) plate and inhibits fibronectin-mediated adhesion of BHK (baby hamster kidney) cells thereon remarkably strongly with 50% inhibition occurring at a 10 ng/mL or 40 pM concentration range.

Animals↗