Anti-HIV-1 activity of an antisense phosphorothioate oligonucleotide bearing imidazole and primary amine groups

Ushijima, Kaoru; Shirakawa, Masahiro; Kagoshima, Koumei; Park, Wee-Sung; Miyano-Kurosaki, Naoko; Takaku, Hiroshi

doi:10.1016/s0968-0896(01)00126-2

Cited by 13 publications

(8 citation statements)

References 45 publications

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“…Applications of artificial ribonucleases in vivo have so far limited to the observation that the phosphorothioate analog of conjugate 33 is a more efficient antisense agent towards HIV-1 gag-mRNA than the corresponding unconjugated sequence. 107 No real breakthrough has been described. The metal ionbased nucleases tend to suffer from time-dependent leakage and exchange reactions of metal ions, which may disturb their intracellular use.…”

Section: Discussionmentioning

confidence: 99%

Artificial ribonucleases

2006

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Mimicking the action of enzymes by simpler and more robust man-made catalysts has long inspired bioorganic chemists. During the past decade, mimics for RNA-cleaving enzymes, ribonucleases, or, more precisely, mimics of ribozymes that cleave RNA in sequence-selective rather than base-selective manner, have received special attention. These artificial ribonucleases are typically oligonucleotides (or their structural analogs) that bear a catalytically active conjugate group and catalyze sequence-selective hydrolysis of RNA phosphodiester bonds.

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Section: Discussionmentioning

confidence: 99%

Artificial ribonucleases

2006

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“…Chart 1 shows the cleaving agents studied (2)(3)(4)(5)(6), their target oligonucleotides (7)(8)(9)(10)(11), and the oligonucleotide standards used for the determination of the cleavage site (12)(13)(14)(15)(16)(17). The cleaving agents are fully 2′-O-methylated oligoribonucleotides bearing the catalytically active [12]aneN 3 chelate tethered either to an abasic sugar unit within the chain (2-4) or to the 3′-terminal hydroxy function (5,6). The or the sequence of the cleaving agent is fully complementary with the 3′-terminal sequence of the target (binding of 5 to 10 or 6 to 11).…”

Section: Structure Of the Cleaving Agents And Theirmentioning

confidence: 99%

Sequence-Selective Cleavage of Oligoribonucleotides by 3d Transition Metal Complexes of 1,5,9-Triazacyclododecane-Functionalized 2‘-O-Methyl Oligoribonucleotides

Niittymäki

Lönnberg

2004

Bioconjugate Chem.

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2'-O-Methyl oligoribonucleotides bearing a 3'-[2,6-dioxo-3,7-diaza-10-(1,5,9-triazacyclododec-3-yl)decyl phospate conjugate group have been shown to cleave in slight excess of Zn(2+) ions complementary oligoribonucleotides at the 5'-side of the last base-paired nucleotide. The cleavage obeys first-order kinetics and exhibits turnover. The acceleration compared to the monomeric Zn(2+) 1,5,9-triazacyclododecane chelate is more than 100-fold. In addition, 2'-O-methyl oligoribonucleotides having the 1,5,9-triazacyclododec-3-yl group tethered to the anomeric carbon of an intrachain 2-deoxy-beta-d-erythro-pentofuranosyl group via a 2-oxo-3-azahexyl, 2,6-dioxo-3,7-diazadecyl, or 2,9-dioxo-3,10-diazatridecyl linker have been studied as cleaving agents. These cleave as zinc chelates a tri- and pentaadenyl bulge opposite to the conjugate group approximately 50 times as fast as the monomeric chelate and show turnover. The cleavage rate is rather insensitive to the length of linker. Interestingly, a triuridyl bulge remains virtually intact in striking contrast to a triadenyl bulge. Evidently binding of the zinc chelate to a uracil base prevents its catalytic action. Replacement of Zn(2+) with Cu(2+) or Ni(2+) retards the cleaving activity of all the cleaving agents tested.

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“…At the beginning of the century, a few reports provided evidence of the successful use of ss-aRNases in cell cultures. It was shown that the conjugate of 2′- O -(2-methoxyethyl) oligonucleotide with the lanthanide macrocyclic complex Eu(THED) 3+ leads to a significant decrease in the level of ICAM-1 protein in endothelial cells [ 81 ], and the ss-aRNase based on the phosphorothioate oligonucleotide and the imidazole residue effectively suppresses the replication of the human immunodeficiency virus HIV-1 in MT-4 cells due to the sequence-specific cleavage of HIV-1 gag mRNA [ 82 ]. These studies demonstrated the superiority of ss-aRNases in comparison with antisense oligonucleotides and the prospects of their use for therapeutic purposes.…”

Section: Therapeutic Application Of Sequence-specific Arnases In Cmentioning

confidence: 99%

Site-Selective Artificial Ribonucleases: Renaissance of Oligonucleotide Conjugates for Irreversible Cleavage of RNA Sequences

et al. 2021

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RNA-targeting therapeutics require highly efficient sequence-specific devices capable of RNA irreversible degradation in vivo. The most developed methods of sequence-specific RNA cleavage, such as siRNA or antisense oligonucleotides (ASO), are currently based on recruitment of either intracellular multi-protein complexes or enzymes, leaving alternative approaches (e.g., ribozymes and DNAzymes) far behind. Recently, site-selective artificial ribonucleases combining the oligonucleotide recognition motifs (or their structural analogues) and catalytically active groups in a single molecular scaffold have been proven to be a great competitor to siRNA and ASO. Using the most efficient catalytic groups, utilising both metal ion-dependent (Cu(II)-2,9-dimethylphenanthroline) and metal ion-free (Tris(2-aminobenzimidazole)) on the one hand and PNA as an RNA recognising oligonucleotide on the other, allowed site-selective artificial RNases to be created with half-lives of 0.5–1 h. Artificial RNases based on the catalytic peptide [(ArgLeu)2Gly]2 were able to take progress a step further by demonstrating an ability to cleave miRNA-21 in tumour cells and provide a significant reduction of tumour growth in mice.

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Anti-HIV-1 activity of an antisense phosphorothioate oligonucleotide bearing imidazole and primary amine groups

Cited by 13 publications

References 45 publications

Artificial ribonucleases

Artificial ribonucleases

Sequence-Selective Cleavage of Oligoribonucleotides by 3d Transition Metal Complexes of 1,5,9-Triazacyclododecane-Functionalized 2‘-O-Methyl Oligoribonucleotides

Site-Selective Artificial Ribonucleases: Renaissance of Oligonucleotide Conjugates for Irreversible Cleavage of RNA Sequences

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