Evaluation of photolyase (Photosome) repair activity in human keratinocytes after a single dose of ultraviolet B irradiation using the comet assay

Photosome is constituted of photolyases included in liposomes. Photolyase is a bacterial enzyme that can repair ultraviolet B (UVB)-induced cyclobutane pyrimidine dimers (CPD) in eukaryotic cells. A modified version of the alkaline comet assay has been set up to evaluate the repair activity of this enzyme after a single dose of UVB (312 nm, 0.06 J/cm2) in human keratinocytes. The formation of single strand breaks (SSB) induced by the UVA photoactivation of the enzyme (1.2 J/cm2) was inhibited by the pretreatment of the cells with 4 mM L-ergothioneine (ERT) during 30 min at 37 degrees C. To increase the sensitivity of the comet assay, an additional lysis was used with a buffer containing sodium dodecyl sulfate (0.5%) and proteinase K (0.1 mg/ml) for 60 min at 37 degrees C. Unrepaired CPD by photolyase were revealed by a second enzymatic treatment with T4 endonuclease V, a CPD specific glycosylase. UVB irradiation increased the SSB level in keratinocytes and additional T4NV treatment enhanced this SSB level by 1.5-2.0-fold confirming that CPD were the major base modifications generated by UVB irradiation. UVA-photoactivated Photosome repaired CPD lesions and decreased the SSB levels by 2.6-3.3-fold. Photosome could be an additional component of sunscreens to reduce the development of skin cancer.     

Regioselective preparation of 5-amino- and 6-amino-1,3-benzoxazole-4,7-diones from symmetrical diaminophenol and aminoresorcinol

Regioisomeric 5-amino- and 6-amino- 1,3-benzoxazole-4,7-diones were prepared from 2,6-diamino-4-methoxyphenol and 2-amino-5-methoxyresorcinol, respectively. These symmetrical precursors have the property to be antisymmetrical to each other with respect to their amino and hydroxy substituents.     

A strategy for isotope containment during radiosynthesis--devolatilisation of bromobenzene by fluorous-tagging-Ir-catalysed borylation en route to the 4-phenylpiperidine pharmacophore

Syntheses of two 4-phenylpiperidines from bromobenzene have been developed involving anchoring to a fluorous-tag, Ir-catalysed borylation, Pd- and Co-catalysed elaboration then traceless cleavage. Although performed using 'cold' (i.e. unlabelled) bromobenzene as the starting material, these routes have been designed to minimise material loss via volatile intermediates and expedite purification during radiosynthesis from 'hot' (i.e. [(14)C] labelled) bromobenzene.     

Synthesis of Double Hydrophilic Block Copolymers Poly(2-isopropyl-2-oxazoline-b-ethylenimine) and their DNA Transfection Efficiency

Gene delivery is now a part of the therapeutic arsenal for vaccination and treatments of inherited or acquired diseases. Polymers represent an opportunity to develop new synthetic vectors for gene transfer, with a prerequisite of improved delivery and reduced toxicity compared to existing polymers. Here, the synthesis in a two-step's procedure of linear poly(ethylenimine-b-2-isopropyl-2-oxazoline) block copolymers with the linear polyethylenimine (lPEI) block of various molar masses is reported; the molar mass of the poly(2-isopropyl-2-oxazoline) (PiPrOx) block has been set to 7 kg mol⁻¹. Plasmid DNA condensation is successfully achieved, and in vitro transfection efficiency of the copolymers is at least comparable to that obtained with the lPEI of same molar mass. lPEI-b-PiPrOx block copolymers are however less cytotoxic than their linear counterparts. PiPrOx can be a good alternative to PEG which is often used in drug delivery systems. The grafting of histidine moieties on the lPEI block of lPEI-b-PiPrOx does not provide any real improvement of the transfection efficiency. A weak DNA condensation is observed, due to increased steric hindrance along the lPEI backbone. The low cytotoxicity of lPEI-b-PiPrOx makes this family a good candidate for future gene delivery developments.     

Calix[4]pyrrole: a new ion-pair receptor as demonstrated by liquid-liquid extraction

Solvent-extraction studies provide confirming evidence that meso-octamethylcalix[4]pyrrole acts as an ion-pair receptor for cesium chloride and cesium bromide in nitrobenzene solution. The stoichiometry of the interaction under extraction conditions from water to nitrobenzene was determined from plots of the cesium distribution ratios vs cesium salt and receptor concentration, indicating the formation of an ion-paired 1:1:1 cesium:calix[4]pyrrole:halide complex. The extraction results were modeled to evaluate the equilibria inherent to the solvent-extraction system, with either chloride or bromide. The binding energy between the halide anion and the calix[4]pyrrole was found to be about 7 kJ/mol larger for cesium chloride than for the cesium bromide. The ion-pairing free energies between the calix[4]pyrrole-halide complex and the cesium cation are nearly the same within experimental uncertainty for either halide, consistent with a structural model in which the Cs+ cation resides in the calix bowl. These results are unexpected since nitrobenzene is a polar solvent that generally leads to dissociated complexes in the organic phase when used as a diluent in extraction studies of univalent ions. Control studies involving nitrate revealed no evidence of ion pairing for CsNO3 under conditions identical to those where it is observed for CsCl and CsBr.     

Synthesis and spectroscopic examination of various substituted 1,3-dibenzoylmethane, active agents for UVA/UVB photoprotection

We describe the synthesis of eighteen variously substituted 1,3- dibenzoylmethane (1,3-DBM) and their change in absorption spectra depending of the nature of donor or acceptor substituents on one or the two aromatic moieties. These compounds were prepared in two steps starting from the corresponding acetophenones, phenol and benzoyl chlorides. The phenyl benzoate was obtained by condensation of benzoyl chloride with phenol in a classical way. Stirring of the phenyl benzoate and acetophenone in DMSO with powdered sodium hydroxide for a few minutes gave the dibenzoylmethane in yields depending on substituents on the phenyl rings. Changes in absorption of UVA/UVB sunlight of these molecules were observed according to the nature and the position of substituents on the phenyl rings. Molecules 2b (1-phenyl-3-(3,4,5-trimethoxyphenyl)-1,3-propanedione), 2d (1-(3,4-dimethoxyphenyl)-3-phenyl-l,3-propanedione), 2e (1-(2,3-dimethoxyphenyl)-3-phenyl-l,3-propanedione) and 2f (1-(2,3,4-trimethoxyphenyl)-3-phenyl-l,3-propanedione) were the most interesting for cosmetic applications because even after irradiation, they preserve their absorptive in UVA range and also in UVB range The other compounds are too photounstable and so can lose their protective effects. These results showed the lack of phototoxicity of these compounds and the possibility to use them as solar filters. Therefore, variously di- or tri methoxy 1,3-DBM are interesting molecules in term of photoprotection and open new prospects for UVA photostable filters.     

Production of WZ events in pp collisions at square root(s) = 1.96 TeV and limits on anomalous WWZ couplings

We present results from a search for WZ production with subsequent decay to l nu l' l' (l and l' = e or mu) using 0.30 fb(-1) of data collected by the D0 experiment between 2002 and 2004 at the Fermilab Tevatron. Three events with WZ decay characteristics are observed. With an estimated background of 0.71 +/- 0.08 events, we measure the WZ production cross section to be 4.5(-2.6)(+3.8) pb, with a 95% C.L. upper limit of 13.3 pb. The 95% C.L. limits for anomalous WWZ couplings are found to be -2.0 < delta kappaZ < 2.4 for form factor scale lambda = 1 TeV, and -0.48 < lambdaZ < 0.48 and -0.49 < delta g(1)(Z) < 0.66 for lambda = 1.5 TeV.     

Measurement of inclusive differential cross sections for pp collisions at (square root)s = 1.96 TeV

We present measurements of the inclusive production cross sections of the Gamma(1S) bottomonium state in pp collisions at (square root)s = 1.96 TeV. Using the Gamma(1S) --> mu(+)mu(-) decay mode for a data sample of 159 +/- 10 pb(-1) collected by the D0 detector at the Fermilab Tevatron collider, we determine the differential cross sections as a function of the Gamma(1S) transverse momentum for three ranges of the Gamma(1S) rapidity: 0 < y(Gamma) < or = 0.6, 0.6 < y(Gamma) < or = 1.2, and 1.2 < y(Gamma) < or = 1.8.     

Measurement of the ratio of B+ and B0 meson lifetimes

The ratio of the B+ and B0 meson lifetimes was measured using data collected in 2002-2004 by the D0 experiment in Run II of the Fermilab Tevatron Collider. These mesons were reconstructed in B-->mu(+)nuD(*-)X decays, which are dominated by B0 and B-->mu(+)nuD 0X decays, which are dominated by B+. The ratio of lifetimes is measured to be tau(+)/tau(0)=1.080+/-0.016(stat)+/-0.014(syst).