Oligonucleotide-europium complex conjugate designed to cleave the 5' cap structure of the ICAM-1 transcript potentiates antisense activity in cells

Baker, Brenda F.; Lot, Sidney S.; Kringel, Jim; Cheng-Flournoy, Shin; Villiet, Pierre; Sasmor, Henri; Siwkowski, Andrew; Chappell, Lara L.; Morrow, Janet R.

doi:10.1093/nar/27.6.1547

Cited by 64 publications

(50 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…24–26 Macrocyclic ligands have also been widely used in biomedical applications as MRI contrast agents, 27, 28 luminescence probes, 29, 30 carriers for drug delivery, 31 and catalysts for selective nucleic acid cleavage. 32 …”

Section: Introductionmentioning

confidence: 99%

Macrocyclization of the ATCUN Motif Controls Metal Binding and Catalysis

2013

View full text Add to dashboard Cite

We report the design, synthesis and characterization of macrocyclic analogs of the amino-terminal copper and nickel binding (ATCUN) motif. These macrocycles have altered pH transitions for metal binding, and unlike linear ATCUN motifs, the optimal cyclic peptide 1 binds Cu(II) selectively over Ni(II) at physiological pH. UV-vis and EPR spectroscopy showed that cyclic peptide 1 can coordinate Cu(II) or Ni(II) in a square planar geometry. Metal binding titration and ESI-MS data revealed a 1:1 binding stoichiometry. Macrocyclization allows for coordination of Cu(II) or Ni(II) as in linear ATCUN motifs, but with enhanced DNA cleavage by the Cu(II)-1 complex relative to linear analogs. The Cu(II)-1 complex was also capable of producing diffusible hydroxyl radicals, which is unique among ATCUN motifs and most other common copper(II) chelators.

show abstract

Section: Introductionmentioning

confidence: 99%

Macrocyclization of the ATCUN Motif Controls Metal Binding and Catalysis

2013

View full text Add to dashboard Cite

show abstract

“…4). It is possible that such forms could also be the result of partial processing of primary transcripts or an attempt by the cell to regulate translation of their mRNAs, as has been observed recently for the ICAM1 gene (Baker et al, 1999).…”

Section: Figmentioning

confidence: 80%

Chromosome localization and characterization of the mouse and human zinc finger protein 265 gene

Adams

Weyden

Kovacic

et al. 2000

Cytogenet Genome Res

View full text Add to dashboard Cite

The chromosome location and pattern of expression of the gene encoding the zinc finger protein 265 (alias “Zis”) in human (ZNF265) and mouse (Zfp265) was determined. By interspecific backcross analysis, we mapped Zfp265 to mouse chromosome 3q. ZNF265 was localized to human chromosome 1p31 by fluorescence in situ hybridization. Since discovery of Zfp265 (in rat) came from studies of changes in renin expression in kidney cell lines, we examined the cell specificity of expression in kidney and also determined hybridization of cDNA with RNA in other tissues. We found that expression was not confined to renin mRNA-containing cells but was ubiquitous. Moreover, the fact that highly conserved homologs of ZNF265p exist in lower organisms (e.g., C4SR in Xenopus), suggests that this protein may have a generalized role in posttranscriptional mechanisms in various cell types and species.

show abstract

“…One of the novel directions in inhibition of oncogenic miRNAs is application of artificial ribonucleases which are conjugates of oligonucleotides complementary targeted to miRNAs and catalytic constructions 10 – 12 . Previously this strategy was used for down-regulation of different viral RNAs 13 , 14 and eukaryotic mRNAs 15 and recently taking into account widespread of miRNA was applied for down-regulation of oncogenic miRNAs 10 , 11 .…”

Section: Introductionmentioning

confidence: 99%

Peptide-oligonucleotide conjugates exhibiting pyrimidine-X cleavage specificity efficiently silence miRNA target acting synergistically with RNase H

Patutina

Bazhenov

Miroshnichenko

et al. 2018

Sci Rep

View full text Add to dashboard Cite

Taking into account the important role of miRNA in carcinogenesis, oncogenic miRNAs are attractive molecules for gene-targeted therapy. Here, we developed a novel series of peptide-oligonucleotide conjugates exhibiting ribonuclease activity targeted to highly oncogenic miRNAs miR-21 and miR-17. When designing the conjugates, we enhanced both nuclease resistance of the targeted oligodeoxyribonucleotide by introducing at its 3′-end mini-hairpin structure displaying high thermostability and robustness against nuclease digestion and the efficiency of its functioning by attachment of the catalytic construction (amide)NH2-Gly(ArgLeu)4-TCAA displaying ribonuclease activity to its 5′-end. Designed miRNases efficiently cleaved miRNA targets, exhibiting Pyr-X specificity, and cleavage specificity had strong dependence on the miRNA sequence in the site of peptide location. In vitro, designed miRNases do not prevent cleavage of miRNA bound with the conjugate by RNase H, and more than an 11-fold enhancement of miRNA cleavage by the conjugate is observed in the presence of RNase H. In murine melanoma cells, miRNase silences mmu-miR-17 with very high efficiency as a result of miR-17 cleavage by miRNase and by recruited RNase H. Thus, miRNases provide a system of double attack of the miRNA molecules, significantly increasing the efficiency of miRNA downregulation in the cells in comparison with antisense oligonucleotide.

show abstract

Oligonucleotide-europium complex conjugate designed to cleave the 5' cap structure of the ICAM-1 transcript potentiates antisense activity in cells

Cited by 64 publications

References 0 publications

Macrocyclization of the ATCUN Motif Controls Metal Binding and Catalysis

Macrocyclization of the ATCUN Motif Controls Metal Binding and Catalysis

Chromosome localization and characterization of the mouse and human zinc finger protein 265 gene

Peptide-oligonucleotide conjugates exhibiting pyrimidine-X cleavage specificity efficiently silence miRNA target acting synergistically with RNase H

Contact Info

Product

Resources

About