Properties of mixed backbone oligonucleotides containing 3′-O-methyl ribonucleosides

Kumar, Prabhat; Takaku, Hiroshi

doi:10.1016/s0960-894x(99)00414-x

Bioorganic & Medicinal Chemistry Letters

1999

DOI: 10.1016/s0960-894x(99)00414-x

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Properties of mixed backbone oligonucleotides containing 3′-O-methyl ribonucleosides

Prabhat Kumar

Hiroshi Takaku

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Cited by 3 publications

References 20 publications

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Metal–bipyridine complexes in DNA backbones and effects on thermal stability

Rodriguez-Ramos

Wilker

2010

J Biol Inorg Chem

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Modified oligonucleotides are showing potential for multiple applications, including drug design, nanoscale building blocks, and biosensors. In an effort to expand the functionality available to DNA, we have placed chelating ligands directly into the backbone of DNA. Between one and three nucleosides were replaced with 2,2'-bipyridine phosphates in 23-mer duplexes of DNA. An array of metal ions were added (Fe(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+), and Pt(2+)) and the influences on duplex stability were examined by melting temperature studies. Titrations and UV-vis absorption spectroscopy were used to provide insights into the nature of the metal complexes formed. We found that Ni(2+) binding to 2,2'-bipyridine typically provided the greatest increase in duplex stability relative to the other metal ions examined. For example, addition of Ni(2+) to one 2,2'-bipyridine-DNA duplex increased the melting temperature by 13 degrees C, from 65.0 +/- 0.3 to 78.4 +/- 0.9 degrees C. These studies show that metal ions and backbone ligands can be used to regulate DNA structure and stability.

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Metal–bipyridine complexes in DNA backbones and effects on thermal stability

Rodriguez-Ramos

Wilker

2010

J Biol Inorg Chem

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Systematic chemical modifications of single stranded siRNAs significantly improved CTNNB1 mRNA silencing

Chang

Pei²,

Guidry

et al. 2016

Bioorganic & Medicinal Chemistry Letters

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Dual or Triple Activation of TLR7, TLR8, and/or TLR9 by Single-Stranded Oligoribonucleotides

Forsbach

Samulowitz

Völp

et al. 2011

Nucleic Acid Therapeutics

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The toll-like receptors (TLRs) 7, 8, and 9 stimulate innate immune responses upon recognizing pathogen nucleic acids. Certain GU- or AU-rich RNA sequences were described to differentiate between human TLR7- and TLR8-mediated immune effects. Those single-stranded RNA molecules require endosomal delivery for stabilization against ribonucleases. We have discovered RNA sequences that preferentially activate TLR7, form higher ordered structures, and do not require specific cellular delivery. In addition, a dual activation of TLR8 and TLR9 without affecting TLR7 can be achieved by chimeric molecules consisting of GU-rich RNA and Cytosin (C) phosphordiester or phosphorthioat (p) guanine (CpG) motif DNA sequences. Such chimeras stimulate TLR9-mediated type I interferon (IFN) and TLR8-depending proinflammatory cytokine and chemokine production upon primary human cell activation. However, an RNA-dependent TLR7 IFN-α cytokine release is suppressed by the phosphorothioate DNA sequence contained in the chimeric molecule. To convert the immune response of a single-stranded RNA from TLR7/8 to TLR9, a simple chemical modification at the 5' end proves to be sufficient. Such 8-oxo-2'-deoxy-guanosine or 8-bromo-2'-deoxy-guanosine modifications of the first guanosine in GU-rich single-stranded RNAs convert the immune response to include TLR9 activation and demonstrate strong additive effects for type I IFN immune responses in human primary cells.

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Properties of mixed backbone oligonucleotides containing 3′-O-methyl ribonucleosides

Cited by 3 publications

References 20 publications

Metal–bipyridine complexes in DNA backbones and effects on thermal stability

Metal–bipyridine complexes in DNA backbones and effects on thermal stability

Systematic chemical modifications of single stranded siRNAs significantly improved CTNNB1 mRNA silencing

Dual or Triple Activation of TLR7, TLR8, and/or TLR9 by Single-Stranded Oligoribonucleotides

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