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91.
Targeted cleavage of polynucleotides by complementary oligonucleotides covalently linked to iron-porphyrins 总被引:13,自引:0,他引:13
Oligothymidylates covalently linked to iron-porphyrins were synthesized to target the nuclease activity of Fe-porphyrin to complementary polynucleotides. In the presence of oxygen and a reducing agent, oligo(dT)7 bearing the reactive group attached to the 3'-phosphate was shown to be active in the cleavage of poly(dA) and poly(rA) but not poly(dT). When poly(dA) was used as a matrix, the reaction yield was higher at low temperature where the complexes are stable; upon increasing temperature, the reaction yield decreased in agreement with the dissociation of the oligonucleotide-polynucleotide complex as measured by absorption spectroscopy. Thus, oligonucleotides covalently linked to iron-porphyrin derivatives can be used to cleave selectively the target sequence of the oligonucleotide. 相似文献
92.
Le Phan Kim Thoa Pai-Shan Chiang Truong Huu Khanh Shu-Ting Luo Tran Ngoc Hanh Dan Ya-Fang Wang Tang Chi Thuong Wan-Yu Chung Nguyen Thanh Hung Jen-Ren Wang Le Nguyen Thanh Nhan Le Quoc Thinh Ih-Jen Su Than Duc Dung Min-Shi Lee 《PloS one》2013,8(7)
Enterovirus 71 (EV71) frequently causes fatal infections in young children in Asia. In 2011, EV71 epidemics occurred in southern Vietnam. We conducted genetic and antigenic analysis of the EV71 isolates and found that 94% of them were genotype C4a related to two lineages circulating in China and 6% were genotype C5 which have circulated in Vietnam since 2003. Antigenic variants were not detected. EV71 vaccines are being developed. Longitudinal enterovirus surveillance data are critical to formulate vaccination policy in Vietnam. 相似文献
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94.
Phuong Thien Thuong Keon Wook Kang Jeong Kee Kim Dae Bang Seo Sang Jun Lee Sung Han Kim Won Keun Oh 《Bioorganic & medicinal chemistry letters》2009,19(6):1815-1817
A MeOH extract of the dry root of Lithospermum erythrorhizon showed strong increasing effect on serine palmitoyltransferase (SPT) in normal human keratinocyte cells (HaCaT cells). Bioassay-guided separation on this extract using repeated chromatography resulted in the isolation of lithospermic acid (1) and two derivative esters, 9″-methyl lithospermate (2) and 9′-methyl lithospermate (3). Compounds 1–3 significantly increased SPT expressions in the relative quantity (%) of SPT1 mRNA as well as SPT2 mRNA. These constituents also raised the level of SPT protein in HaCaT cells in a dose-dependent manner, with the increased level of SPT protein in HaCaT cells of 55%, 23%, and 81% at the concentration of 100 μg/ml, respectively. This finding suggests that lithospermic acid and its derivatives from L. erythrorhizon might improve the permeability barrier by stimulating the protein level of SPT. 相似文献
95.
C. Fini V. Dinh Thuong M. Aliante A. Floridi S. Cannistraro 《The Journal of membrane biology》1994,142(1):137-144
Seminal plasma separated from freshly ejaculated bull semen contains vesicles with a 5-nucleotidase activity incorporated as an ectoenzyme anchored by glycosyl phosphatidylinositol (GPI). After its extraction from bull seminal plasma vesicles, the protein was purified and reconstituted into hen egg yolk lecithin liposomes obtained through prolonged dialysis of buffered n-octylglucoside detergent solutions of lipid, protein and various effectors against detergent-free solutions. Gel filtration experiments showed that the enzyme incorporated into liposomes in a dimeric form with its two subunits linked by disulfide bridges. In the presence of reduced glutathione, the protein dissociated into monomers and failed to incorporate into liposomes. Electron spin resonance (ESR) experiments, performed with liposomes containing electron spin labels localized at the hydrophilic lipid headgroups (5-doxyl stearic acid) or in the hydrophobic lipid hydrocarbon chains (16-doxyl stearic acid), demonstrated that the incorporation of 5-nucleotidase resulted in the immobilization of the spin probes. Furthermore, the spectral parameters obtained before and after treatment of 5-nucleotidase-containing liposomes with phosphatidylinositol-specific phospholipase C (PI-PLC) indicated that the liposome membrane bilayer did not contain protein segments. This supports the well-known ecto-localization of 5-nucleotidase and rules out a previously reported possibility of a proteic transmembrane anchoring of the enzyme.We thank Mr. Marcello Coli and Dr. Maria Grazia Cantelmi, University of Perugia, for their skillful technical assistance; Dr. Paolo Ghinassi and Dr. Franca Farabegoli, Semen Italy, Diegaro, Cesena, Italy and Dr. Augusto Chiacchierini, Centro Tori Perugia, Italy, for kindly supplying the bull semen; Dr. Maria Grazia Rambotti, Department of Experimental Medicine, University of Perugia, Italy, for her skillful assistance in the electron microscopy experiments; Ms. Darlene I. Morosi for her helpful suggestions. 相似文献
96.
Dao TT Dang TT Nguyen PH Kim E Thuong PT Oh WK 《Bioorganic & medicinal chemistry letters》2012,22(11):3688-3692
The emergence of the H1N1 swine flu pandemic has the possibility to develop the occurrence of disaster- or drug-resistant viruses by additional reassortments in novel influenza A virus. In the course of an anti-influenza screening program for natural products, 10 xanthone derivatives (1-10) were isolated by bioassay-guided fractionation from the EtOAc-soluble extract of Polygala karensium. Compounds 1, 3, 5, 7, and 9 with a hydroxy group at C-1 showed strong inhibitory effects on neuraminidases from various influenza viral strains, H1N1, H9N2, novel H1N1 (WT), and oseltamivir-resistant novel H1N1 (H274Y) expressed in 293T cells. In addition, these compounds reduced the cytopathic effect of H1N1 swine influenza virus in MDCK cells. Our results suggest that xanthones from P. karensium may be useful in the prevention and treatment of disease by influenza viruses. 相似文献
97.
Vinogradov S Roig V Sergueeva Z Nguyen CH Arimondo P Thuong NT Bisagni E Sun JS Hélène C Asseline U 《Bioconjugate chemistry》2003,14(1):120-135
DNA binding compounds, such as benzo[e] (BePI) and benzo[g] pyridoindole (BgPI) derivatives, exhibit preferential stabilization of triple helices. We report here the synthesis of a series of pyrimidine triple-helix-forming oligo-2'-deoxyribonucleotides conjugated with these molecules. BePI was coupled to the 5-position of 2'-deoxyuridine via two linkers of different sizes attached to its 11-position and placed at either the 5'-end, inside the sequence, or at both the 5'-end and the internal positions using periodate oxidation of a diol-containing oligonucleotide followed by reductive coupling with amino-linked BePI. The same BePI derivatives were also linked to the oligonucleotide chain via internucleotidic phosphorothiolate or phosphoramidate linkages. A mixture of diastereoisomers was prepared as well as separate pure Rp and Sp isomers. A BePI derivative, with two different linkers attached to its 3-position, and BgPI derivatives were also linked to the 5-position of a 2'-deoxyuridine located at either the 5'-end or inside the sequence, as well as to the beta- anomeric position of an additional 2'- deoxyribose placed inside the sequence. The binding properties of these oligonucleotide-benzopyridoindoles conjugates with their double-stranded DNA target was studied by absorption spectroscopy. 相似文献
98.
Short modified antisense oligonucleotides directed against Ha-ras point mutation induce selective cleavage of the mRNA and inhibit T24 cells proliferation. 总被引:15,自引:1,他引:14
T Saison-Behmoaras B Tocqu I Rey M Chassignol N T Thuong C Hlne 《The EMBO journal》1991,10(5):1111-1118
We have used derivatized antisense oligodeoxynucleotides both in vitro and in vivo specifically to inhibit translation of the activated human oncogene Ha-ras. The oligonucleotides (5'-CCACACCGA-3') were targeted to a region of Ha-ras mRNA including the point mutation G----T at the 12th codon which leads to a Gly----Val substitution in the ras p21 protein. They were linked to an intercalating agent and/or to a hydrophobic tail, both to increase their affinity for their mRNA target and to enhance their uptake by tumor cells. A cell-free translation system was used to demonstrate an RNase H-dependent specific inhibition of activated ras protein synthesis. 50% inhibition was observed at a concentration of 0.5 microM of the most efficient oligonucleotide (5'-substitution with an acridine derivative and 3'-substitution by a dodecanol chain). This inhibitory effect stems from a point mutation-sensitive cleavage of the mRNA and it mirrors the growth inhibition obtained with T24 bladder carcinoma cells, which carry activated Ha-ras. The proliferation of HBL100 cells (non tumorigenic human mammary cell line) which carry two copies of normal Ha-ras was unaffected. This study shows that it is possible to design antisense agents that will inactivate the mutated oncogene but not the protooncogene which is generally essential to cell survival. 相似文献
99.