ArticleACS chemical biology2010
Minor-groove-modulating adenosine replacements control protein binding and RNAi activity in siRNAs.
Article in ACS chemical biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Synthesis of Nucleobase-Modified RNA Oligonucleotides by Post-Synthetic Approach.Molecules (Basel, Switzerland) · 2020Review
- Therapeutic siRNA: state of the art.Signal transduction and targeted therapy · 2020Review
- Double Nitroxide Labeling by Copper-Catalyzed Azide-Alkyne Cycloadditions with Noncanonical Amino Acids for Electron Paramagnetic Resonance Spectroscopy.ACS chemical biology · 2019Article
- Conjugation and Evaluation of Small Hydrophobic Molecules to Triazole-Linked siRNAs.ACS medicinal chemistry letters · 2015Article
- Base modification strategies to modulate immune stimulation by an siRNA.Chembiochem : a European journal of chemical biology · 2015Article
- Short interfering RNA guide strand modifiers from computational screening.Journal of the American Chemical Society · 2013Article
- Chemical architecture and applications of nucleic acid derivatives containing 1,2,3-triazole functionalities synthesized via click chemistry.Molecules (Basel, Switzerland) · 2012Review
- Promiscuous 8-alkoxyadenosines in the guide strand of an siRNA: modulation of silencing efficacy and off-pathway protein binding.Journal of the American Chemical Society · 2012Article
- 7-Substituted 8-aza-7-deazaadenosines for modification of the siRNA major groove.Organic & biomolecular chemistry · 2012Article
- Novel modifications in RNA.ACS chemical biology · 2012Review
- Chemical modification of siRNA bases to probe and enhance RNA interference.The Journal of organic chemistry · 2011Review
- Nucleobase and ribose modifications control immunostimulation by a microRNA-122-mimetic RNA.Journal of the American Chemical Society · 2011Article
- 8-Oxoguanosine switches modulate the activity of alkylated siRNAs by controlling steric effects in the major versus minor grooves.Journal of the American Chemical Society · 2011Article
- Review
- Synthesis of N2-alkyl-8-oxo-7,8-dihydro-2'-deoxyguanosine derivatives and effects of these modifications on RNA duplex stability.The Journal of organic chemistry · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Short-interfering RNAs (siRNAs) are common tools in molecular biology; however, the development of RNAi-based therapeutics is limited by immunostimulatory and nonspecific effects mediated by off-target RNA-binding proteins. The RNA-dependent protein kinase (PKR) and adenosine deaminase that acts on RNA 1 (ADAR1) are two proteins implicated in RNAi off-target effects and share a common means of interaction with siRNAs through double-stranded RNA binding motifs (dsRBMs). Here we report the site-specific introduction of N²-propargyl 2-aminopurine into siRNAs and subsequent conversion to two bulky products via copper-catalyzed azide alkyne cycloaddition (CuAAC) with either N-azidoacetyl-mannosamine azide or N-ethylpiperidine azide. We observed position-specific effects on RNAi activity for modifications made to both the passenger and guide strands. These findings are rationalized in light of recent structural studies of components of the RNA-induced silencing complex (RISC) and RISC-loading complex (RLC). The most active siRNAs were assayed for binding affinity to PKR and ADAR1. PKR binding was significantly reduced by multiple modifications, regardless of size, and ADAR1 binding was reduced in a position- and size-sensitive manner. Our findings present a strategy for designing siRNAs that reduce off-target dsRBM-protein binding while retaining native RNAi activity.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.