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Accueil > Publications > Recherche par années > Années 2000 > 2007

2007

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A minimalistic approach to identify substrate binding features in B1 Metallo-ß-lactamases

The 2-oxoazetidinylacetate sodium salt was synthesized as a model of a minimal P-lactam drug. This compound and the monobactam aztreonam were assayed as substrates of the Metallo-p-lactamase Bell. None of them was hydrolyzed by the enzyme. While the azetidinone was not able to bind Bell, aztreonam was shown to bind in a nonproductive mode. These results provide an explanation for the unability of Metallo-ß-lactamases to inactive monobactams and give some clues for inhibitor design. (c) 2007 Elsevier Ltd. All rights reserved.

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A topological mechanism for TRF2-enhanced strand invasion

Telomeres can fold into t-loops that may result from the invasion of the 3’ overhang into duplex DNA. Their formation is facilitated in vitro by the telomeric protein TRF2, but very little is known regarding the mechanisms involved. Here we reveal that TRF2 generates positive supercoiling and condenses DNA. Using a variety of TRF2 mutants, we demonstrate a strong correlation between this topological activity and the ability to stimulate strand invasion. We also report that these properties require the combination of the TRF-homology (TRFH) domain of TRF2 with either its N- or C-terminal DNA-binding domains. We propose that TRF2 complexes, by constraining DNA around themselves in a right-handed conformation, can induce untwisting of the neighboring DNA, thereby favoring strand invasion. Implications of this topological model in t-loop formation and telomere homeostasis are discussed.

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Alkyne-azide click chemistry mediated carbanucleosides synthesis

Hitherto unknown 1,4-disubstituted-[1,2,3]-triazolo-4’,4’-dihydroxymethyl-3’-deoxycarbanucleosides were synthesized based on a "click approach." Various alkynes were introduced on a key azido intermediate by the "click" 1,3-dipolar Huisgen cycloaddition. Their antiviral activities and cellular toxicities were evaluated on vaccinia virus. None of the synthesized compounds exhibited a significant antiviral activity.

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Anomalous diffusion of water in [BMIM][TFSI] room-temperature ionic liquid

We have studied the self-diffusion properties of butyl-methyl-imidazolium bis(trifluoromethylsulfonyl)-imide ([BMIM][TFSI]) + water system. The self-diffusion coefficients of cations, anions, and water molecules were determined by pulsed field gradient NMR. These measures were performed with increased water quantity up to saturation (from 0.3 to 30 mol %). Unexpected variations have been observed. The self-diffusion coefficient of every species increases with the quantity of water but not in the same order of magnitude. Whereas very similar evolutions are observed for the anion and cation, the increase is 25 times greater for water molecules. We interpret our data by the existence of phase separation at microscopic scale.

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Bees and systemic insecticides (imidacloprid, fipronil) in pollen : subnano-quantification by HPLC/MS/MS and GC/MS.

Imidacloprid and fipronil are two insecticides acting on the central nervous system. They are used worldwide, from the mid nineties, especially for seed coating of crops. Concomitantly to their introduction and their increasing use in French fields, honeybee populations decreased. Bee problems are nowadays reported in other countries (also called disappearing disease, desplobación de las colmenas, trouble des abeilles, deperimento degli apiari or colony collapse disorder). Bee problems have certainly several origins. Contamination of pollen and nectar by such chemicals appeared as one of the most probable cause, since subletal effects and chronic intoxications were observed on bees, at very low concentrations. We developed fully validated methods to measure contamination in pollen (sunflower and maize) for imidacloprid (HPLC/MS/MS) and for fipronil and 3 of its derivatives (GC/MS). For imidacloprid LOD and LOQ are 0.3 and 1 ng/g, respectively. For fipronil and each derivative (fiprole), LOD and LOQ are 0.07 and 0.2 ng/g, respectively. The averaged level of imidacloprid in pollen was 2-3 ng/g, which is 20-30 times higher than the concentration inducing significant mortality by chronic intoxication. Fiproles were detected in 48% of pollens issuing from treated crops. Fipronil and its sulfone derivative represented 77% and 17% of contaminants, respectively. The averaged fiprole sum Σf was 0.3 - 0.4 ng/g, which is 30-40 times higher than the concentration inducing significant mortality of bees by chronic intoxication.

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Bending and unwinding of nucleic acid by prion protein

Nucleic acid induces conformational changes in the prion protein (23-231 amino acids) to a structure resembling its pathological isoform. The prion protein, in turn, facilitates DNA strand transfer and acts as a DNA chaperone which is modulated by the N-terminal unstructured basic segment of the protein. Here we have studied the prion protein induced conformational changes in DNA using oligonucleotides covalently labeled with the energy donor fluorescein and the acceptor rhodamine moieties by fluorescence resonance energy transfer (FRET) and by thermal stability of the unlabeled oligonucleotides. The protein induces a strong FRET effect in the oligonucleotides evidenced from the simultaneous quenching of fluorescence intensity of the donor and increase in the fluorescence intensity of the acceptor, which indicate bending of the oligonucleotides by the prion protein.

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