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1.
Hirofumi Furusho Takahiro Ogata Akihisa Kato Yoshie Sato Tohru Endo Akira Kaji 《Nucleosides, nucleotides & nucleic acids》2013,32(4):739-753
Abstract Several acyclic analogues of guanosine, 2′-deoxy-2′, 3′-secoguanosine(3), 3′-deoxy-2′, 3′-secoguanosine (4), and 2′-, 3′-dideoxy-2′-, 3′-secoguanosine were synthesized from guanosine. In addition, the 3′-, 5′-cyclic phosphate (21) and 3′-, 5′-cyclic methylphosphonates (22a, b) of 3 were also prepared. At concentrations up to 300 μM none of these compounds had significant antiherpetic activity in antiviral assays in vitro. 相似文献
2.
Mechanism of vesicular stomatitis virus mRNA decay 总被引:4,自引:0,他引:4
The chemical and functional stability of the five vesicular stomatitis virus (VSV) messenger RNAs during infection of Chinese hamster ovary (CHO) cells was studied using the temperature-sensitive mutant, tsG114. By incubating infected cells at the nonpermissive temperature (39 °C), RNA synthesis was blocked and the five VSV mRNAs decayed chemically and functionally with a half-life of 1 to 1.5 h. However, all five VSV mRNAs were stable in vivo at 39 °C when protein synthesis was blocked with either cycloheximide or emetine. In contrast, when pactamycin was used to inhibit protein synthesis, the chemical and functional decay rates of the VSV mRNAs were indistinguishable from those observed in the absence of antibiotic. On the basis of the mode of action of each of the antibiotic inhibitors, these data imply that (a) ribosome movement along VSV mRNAs plays no role in their stabilities, and (b) each VSV mRNA contains a nuclease-sensitive site, at its 5′ end at or near the initiation site, which regulates its decay in vivo. 相似文献
3.
Yasuhide Hirota Yujiro Arao Akiko Matsumoto Shiro Nii Yusuke Wataya 《Nucleosides, nucleotides & nucleic acids》2013,32(9-10):2079-2087
Abstract The effect of (E)-5-(2-bromovinyl)-2′-deoxyuridine (BVDU) on deoxyribonucleoside 5′-triphosphate pools was studied in cells transfected with gene for thymidine kinase of herpes simplex virus type 1 and cells infected with the virus. When infected cells were treated with BVDU, the triphosphate form of the nucleoside analog was detected. When transfected cells were treated with BVDU, the triphosphate form was not detected and the pattern of changes in the pools was the same as after 5-fluoro-2′-deoxyuridine treatment. BVDU seems to inhibit DNA synthesis differently in the two cell lines and nucleotide metabolism in the transfected cells was not the same as in the infected cells. 相似文献
4.
Abstract We synthesized and analyzed DNA hairpin molecules with methylphosphonate linkages of defined stereochemistry in the loop region. Dinucleotide building blocks ApA and TpT (p indicating methylphosphonate linkage with either Rp or Sp configuration) were synthesized, separated into the diastereomers, and incorporated at three positions of the tetraloops 5′-CGCAAAAGCG-3′ and 5′-CGCTTTTGCG-3′. The oligonucleotides were analyzed for their melting behavior. With a Tm of 67.5°C the molecule 5′-CGCAAApAGCG-3′ with a Sp configurated methylphosphonate is distinctly more stable than the Rp configurated one (Tm = 60.5 °C) and the unmodified oligonucleotide (Tm = 64.5 °C). In contrast to double helical DNA where the substitution of a phosphorodiester by a Sp configurated methylphosphonate results in a lower Tm, in DNA hairpin the introduction of Sp and Rp methylphosphonates at specific positions can lead to a stabilization of the structure. 相似文献
5.
Rakesh Kumar Edward E. Knaus Leonard I. Wiebe 《Nucleosides, nucleotides & nucleic acids》2013,32(6):1219-1228
Abstract Reaction of the 5′-O-t-butyldimethylsilyl derivatives of thymidine and 2′-deoxyuridine with the Vilsmeier reagent (POCI3/DMF), and removal of the t–butyldimethylsilyl protecting group, afforded 3′-O-formylthymidine (5) and 3′-O-formyl-2′-deoxyuridine (6), respectively. In vitro evaluation, determined as the ability of the test compound to inhibit HIV induced cytopathogenicity in CEM cells, indicated that 5 was moderately active, whereas 6 was inactive. 相似文献
6.
7.
Suhaib M. Siddiqi Xing Chen Stewart W. Schneller 《Nucleosides, nucleotides & nucleic acids》2013,32(3-4):267-278
Abstract Beginning with the treatment of the diacetate of cis-3,5-cyclopentenediol (5) with Pseudomonas cepacia lipase, (-)-5′-noraristeromycin (1) and (-)-7-deaza 5′-noraristeromycin (3) have been prepared. Subjecting 5 to treatment with porcine liver esterase led to an efficient preparation of a substituted cyclopentane precursor which, following literature precedence, can be converted into (-)-5′-homoaristeromycin (4). 相似文献
8.
I. Robbins J. E. Gee G. Mitta B. Rayner S. Vichier-guerre M. Leng 《Nucleosides, nucleotides & nucleic acids》2013,32(6-7):1667-1668
Abstract Most second-generation ON antisense analogs do not activate RNase H. Alternative strategies to arrest translation in a reticulocyte cell-free assay programmed by VSV mRNAs have been explored. 相似文献
9.
Eric S. Gibson Krystyna Lesiak Kyoichi A. Watanabe Lorraine J. Gudas Krzysztof W. Pankiewicz 《Nucleosides, nucleotides & nucleic acids》2013,32(3):363-376
Abstract A synthesis of the C-nucleoside, 2-amino-7-(2-deoxy-β-D-erythro-pentofuranosyl)-3H,5H-pyrrolo[3,2-d]pyrimidin-4-one (9-deaza-2′-deoxyguanosine) was achieved starting from 2-amino-6-metnyl-3H-pyrimidin-4-one (5) and methyl 2-deoxy-3,5-di-O-(p-nitrobenzoyl)- D-erythro-pento-furanoside (11). The anomeric configuration of the C-nucleoside was established by 1H NMR, NOEDS and ROESY. This C-nucleoside did not inhibit the growth of T-cell lymphoma cells. 相似文献
10.
P S Miller C H Agris L Aurelian K R Blake A Murakami M P Reddy S A Spitz P O Ts'o 《Biochimie》1985,67(7-8):769-776
Oligodeoxyribonucleoside methylphosphonates contain nonionic 3'-5' linked methylphosphonate internucleotide bonds in place of the normal charged phosphodiester linkage of natural nucleic acids. These oligomers are resistant to nuclease hydrolysis, can pass through the membranes of mammalian cells in culture and can form stable hydrogen-bonded complexes with complementary nucleotide sequences of cellular RNAs such as mRNA. The oligomers are readily synthesized on insoluble polymer supports. Their chainlength and nucleotide sequence can be determined by chemical sequencing procedures. Oligonucleoside methylphosphonates which are complementary to the 5'-end, initiation codon region, or coding region of rabbit globin mRNA inhibit translation of the mRNA in rabbit reticulocyte lysates and globin synthesis in rabbit reticulocytes. This inhibition is due to the interaction of the oligomers with mRNA and the extent of inhibition is influenced by the secondary structure of the mRNA and the location of oligomer binding site on the mRNA. Oligomers complementary to the initiation codon regions of N, NS and G protein mRNAs of Vesicular stomatitis virus (VSV) inhibit virus protein synthesis in VSV-infected Mouse L-cells. These oligomers do not affect L-cell protein synthesis or growth. Virus protein synthesis and growth can also be selectively inhibited by oligonucleoside methylphosphonates which are complementary to the donor or acceptor splice junctions of virus pre mRNA. An oligomer complementary to the donor splice junction of SV40 large T antigen mRNA inhibits T-antigen synthesis in SV40-infected African green monkey kidney cells but does not inhibit overall cellular protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
11.
Tomoharu Iino Satoshi Shuto Akira Matsuda 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):169-181
Abstract A synthetic method for (2′S)-2′-C-alkyl-2′-deoxyuridines (9) has been described. Catalytic hydrogenation of 1-[2-C-alkynyl-2-O-methoxalyl-3,5-O-TIPDS-β-D-arabino-pentofuranosyl]uracils (5) gave 1-[2-C-(2-alkyl)-2-O-methoxalyl-3,5-O-TIPDS-β-D-arabino-pentofuranosyl]uracils (4) as a major product, which were then subjected to the radical deoxygenation, affording (2′S)-2′-alkyl-2′-deoxy-3′,5′-O-TIPDS-uridines (7) along with a small amount of their 2′R epimers. 相似文献
12.
T. Sudhakar Rao Robert F. Rando John H. Huffman Ganapathi R. Revankar 《Nucleosides, nucleotides & nucleic acids》2013,32(9-10):1997-2008
Abstract In this paper we describe a practical synthesis of 5-nitro-2′-deoxyuridine (4) and 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-nitrouracil (11). These compounds were then evaluated for their ability to inhibit the growth of human cytomegalovirus (HCMV, strain AD169) in MRC-5 cells using a plaque reduction assay. Compound 11 was unable to inhibit the growth of HCMV at the highest concentration tested (100 μg/mL). However, compound 4 (5-NO2-dU) exhibited marginal activity against HCMV in vitro in a dose-dependent manner with a 50% inhibitory concentrations (IC50) of 1 to 5 μg/mL. Combinations of 5-NO2-dU with ganciclovir synergistically inhibited HCMV induced cell killing in culture. 相似文献
13.
Kaoru Hisa Atsushi Kittaka Hiromichi Tanaka Kentaro Yamaguchi ) Tadashi Miyasaka 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):85-96
Abstract Radical reactions of 5′-O-(2-bromo-1-methoxy)ethyl- and 5′-O-(2-propynyl)-2′,3′-dideoxy-2′,3′-didehydrouridines were investigated. Both reactions proceeded in a 6-exo-trig manner to give products cyclized regio- and stereospecifically at the 3′-position. The structures of these products were analyzed by X-ray crystallography. 相似文献
14.
《Nucleosides, nucleotides & nucleic acids》2013,32(5-8):1627-1629
Abstract A series of oligonucleotide conjugates were designed and synthesized as novel inhibitors of human telomerase. These compounds contain a relatively short (6–7-mer) oligonucleotide domain, with an N3′ → P5′ phosphoramidate (np) or thio-phosphoramidate (nps) backbone, targeted to the template region of the RNA component of the enzyme and various pendant groups attached to either their 5′- or preferably to the 3′- termini. The most potent compounds in the series inhibited telomerase with low nM IC50 values in biochemical assays whereas the cognate oligonucleotides without the pendant groups were significantly less active having IC50 values 100-1000-fold higher. 相似文献
15.
Janice R. Sufrin Arthur J. Spiess John F. Karny Debora L. Kramer Robert G. Hughes Jr Ralph J. Bernacki 《Nucleosides, nucleotides & nucleic acids》2013,32(4):505-514
Abstract A novel synthesis of the nucleoside analog, 5′-deoxy-5′-(cyclopropylmethylthio)adenosine (CPMTA, 1) has been developed. CPMTA is a closely related structural analog of 5′-deoxy-5′-(isobutylthio)-adenosine (SIBA, 2), which has been widely studied and shown to exert a multitude of biological effects. The in vitro and in vivo antitumor (L1210 leukemia) activity of CPMTA has been found to be comparable to that of SIBA, whereas its in vitro antiviral (HSV and VSV) activity is diminished. These agents are being developed as inhibitors of methylation and/or polyamine synthesis. 相似文献
16.
Abstract 2′-Deoxy-5′-0-(4,4′-dimethoxytrityl)-5-methyl-N 4-(1-pyrenylmethyl)-α-cytidine (5) was prepared by reaction of 1-pyrenylmethylamine with an appropriate protected 4-(l,2,4-triazolyl)-α-thymidine derivative 3 which was synthesized from 5-O-DMT protected α-thymidine 1. Aminolysis of 3 afforded 3′-O-acetyl-2′-deoxy-5′-O-(4,4′-dimethoxytrityl)-5-methyl-α-cytidine (8). Benzoylation of 8 and removal of acetyl afforded N 4-benzoyl-2-deoxy-5–0-(4,4′-dimethoxytrityl)-5-methyl-α-cytidine (10). The amidites of compounds 5and 10 were prepared and used in α-oligonucleotide synthesis. DNA three-way junction (TWJ) is stabilized when an α-ODN is used for targeting the dangling flanks of the stem in a DNA hairpin. Further stabilization of the TWJ is observed when 5 is inserted into the α-ODN at the junction region. 相似文献
17.
Akira Matsuda Yuki Nakajima Tohru Ueda Takuma Sasaki 《Nucleosides, nucleotides & nucleic acids》2013,32(2-4):237-246
Abstract Reaction of 1-(3,5-Otetraisopropyldisiloxan-1,3-diyl-β-D-erythro-2-pentofuran-2-ulosyl)uracil (8) with hydroxylamine hydrochloride in pyridine at room temperature for 24 h or at 80°C for 3 h gives the 2′-deoxy-2′-hydroxyiminouridine derivative 9 in good yield. Similarly, oximation of 8 with methoxyamine has been done to obtain 2′-deoxy-2′-methoxyimino derivatives 11 in a high yield. Compound 9 was converted into 1-(2-deoxy-2-hydroxyimino-β-D-erythro-pentofuranosyl)cytosine (3). Cytotoxicity in vitro of these nucleosides against murine leukemia L1210 cells was also examined. 相似文献
18.
David Dukhan Florence De Valette Roland Marquet Bernard Ehresmann Chantal Ehresmann François Morvan 《Nucleosides, nucleotides & nucleic acids》2013,32(6-7):1423-1424
Abstract in the present paper, we describe the synthesis of a modified 9-mer oligonucleotide, 4′-S-r(UGUGCACCU) containing for the first time 4′-thio-guanosine units. This modified 9-mer was found to inhibit in vitro genomic RNA dimerization as well as the wild type RNA. 相似文献
19.
Aki Tomikawa Masaki Seno Kunie Sato‐Kiyotaki Chizuru Ohtsuki Toshialu Hirai Toyofumi Yamaguchi 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):487-501
Abstract Starting from 2′,3′,5′-tri-O-acetyl-2-iodoadenosine, 9-(β-D-arabinofuranosyl)-2-(p-n-butylanilino)adenine and its 2′(S)-azido counterparts were synthesized in seven steps. These exhibited only moderate growth-inhibitory effects against mouse leukemic P388 cells (IC50 = 13–24 μM), although 5′-triphosphate derivatives showed strong and selective inhibitory action on calf thymus DNA polymerase α, but not on β- and ?-polymerases from eukaryotes. 相似文献
20.
Hiroshi Shiragami Yusuke Amino Yutaka Honda Masayuki Arai Yasuhiro Tanaka Hisao Iwagami 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):31-45
Abstract Practical method to produce 2′,3′-dideoxypurinenucleosides from 9-(2,5-di-O-acetyl-3-bromo-3-deoxy-β-D-xylofuranosyl)purines (1) was developed. High ratio of 2′,3′-dideoxynucleoside to 3′-deoxyribonucleoside was obtained by selecting the reaction conditions (solvent, pH and/or base), or changing 2′-acyloxy leaving group. The reaction mechanism was studied by deuteration experiments of 1a and 1-(3,5-di-O-acety1-2-bromo-2-deoxy-β-D-ribofuranosyl)thymine (12). 相似文献