Nucleosides & nucleotides最新文献

HIV-1 DNA integration is carried out by integrase, a viral protein which binds to specific sequences located on both extremities of the HIV-1 DNA LTR. Inhibition of integration was observed with submicromolar concentrations of mono- or bifunctionalized 11-mer oligonucleotide-intercalators, which were designed to form an alternate strand triple helix with the U5 LTR end containing two adjacent purine tracts on opposite strands 5'-GGAAAATCTCT-3'/3'-CCTTTTAGAGA-5'.

Oligonucleotides (ODNs) conjugated to rhodamin (Rh) and 4-[(N-2-chloroethyl-N-methyl)amino] benzylamine were used to investigate ODNs transport into keratinocytes. Affinity labeling of two proteins, 63 and 35 kDa, and the inhibition of the affinity labeling and ODNs uptake by the cells in the presence of nucleic acids, polyanions and trypsin suggest, that the proteins are involved in transport of nucleic acids in keratinocytes.

Magnesium (Mg2+) potentiated the anti-vesicular stomatitis virus (VSV) activity of poly r(A-U) or poly r(G-C) and the anti-HIV-1 activity of poly r(A-U). Mg2+ did not affect the anti-VSV activity of poly (rI).poly (rC), poly (dA-dT).poly (dA-dT) or poly (dG-dC).poly (dG-dC). Modulation of one or more nuclear (nucleolar) processes of the host cell may be responsible for the synergistic antiviral activity.

I provide a brief review and perspective thoughts concerning the antisense oligonucleotide, drug discovery paradigm.

DNA probe arrays were synthesized with analogs of 2,6-diaminopurine and 2'-O-methyl-thymidine in place of A and T. AT-rich GeneChip test arrays containing 14-mer or 20-mer analog probes improved hybridization to fluorescently-labeled RNA sequences under stringent conditions.

Three new cholesterol-containing phosphoramidites where synthesized and used in automated synthesis of modified DNA fragments. These cholesterol lesions are good substrates for the E. coli UvrABC endonuclease. In vitro they are incised from damaged DNA with higher efficiency in respect with the cholesterol lesions previously published.

The cytotoxicity of anti-PAI-5 hexadecanucleotides (phosphodiesters and phosphorothioates) and their conjugates with lipophilic alcohols was tested in EA.hy 926 hybrid endothelial cells. Some cytotoxicity was found for cholesteryl and bornyl conjugates at concentrations higher than those used for antisense inhibition experiments.

We have demonstrated that antisense phosphorothioate oligonucleotides (S-ODNs) inhibit influenza virus A replication in MDCK cells. The liposomally encapsulated and the free antisense phosphorothioate oligonucleotides with four target sites (PB1, PB2, PA, and NP) were tested for their abilities to inhibit virus-induced cytopathogenic effects by a MTT assay using MDCK cells. The liposomally encapsulated S-ODN complementary to the sites of the PB2-AUG initiation codon showed highly inhibitory effects. Therefore, the antiviral effects of S-ODN-PB2-AUG and PA-AUG were examined in a mouse model of influenza virus A infection. PB2-AUG oligomer treated i.v. significantly prolonged the mean survival time in day (MDS) and increased the survival rates with does dependent manner.

NMR spectroscopy was used to determine the solution structures of RNA oligonucleotides comprising the anticodon domain of tRNA(Lys,3). The structural effects of the pseudouridine modification at position 39 were investigated and are well correlated with changes in thermodynamic parameters. The loop conformation differs from that seen in tRNA(Phe) and provides an explanation of the critical role of modification in this tRNA.

Synthesis of a number of photoactive thiopurine-containing nucleosides was described. S-methylation of the synthesized compounds in the course of the reaction catalyzed by recombinant human thiopurine S-methyltransferase was studied by UV-spectroscopy.