Evidence map›Paper›PMID 41318945›Full record

ArticleChemistry (Weinheim an der Bergstrasse, Germany)2026

Synthesis of 2'-O,4'-Cα-Dimethyl Ribonucleoside Analogs and Their Effects on RNA and Modulation of ADAR Editing.

Victorio Jauregui-Matos, Hannah F Brinkman, Prince J Salvador, Olivia Jacobs, Jeff Cheng, Sukanya Mozumder, Tyson Vu, Andrew J Fisher, Peter A Beal

Abstract read
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In one paragraph

Article in Chemistry (Weinheim an der Bergstrasse, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Victorio Jauregui-MatosDepartment of Chemistry, University of California, Davis, California, USA.ORCID https://orcid.org/0000-0003-2009-5521
Hannah F BrinkmanDepartment of Chemistry, University of California, Davis, California, USA.ORCID https://orcid.org/0000-0003-3463-4573
Prince J SalvadorDepartment of Chemistry, University of California, Davis, California, USA.ORCID https://orcid.org/0000-0003-4536-584X
Olivia JacobsDepartment of Chemistry, University of California, Davis, California, USA.ORCID https://orcid.org/0009-0002-8577-9000
Jeff ChengDepartment of Chemistry, University of California, Davis, California, USA.ORCID https://orcid.org/0000-0002-2846-3205
Sukanya MozumderDepartment of Chemistry, University of California, Davis, California, USA.ORCID https://orcid.org/0000-0002-2308-8741
Tyson VuDepartment of Chemistry, University of California, Davis, California, USA.ORCID https://orcid.org/0009-0004-8671-4967
Andrew J FisherDepartment of Chemistry, University of California, Davis, California, USA.ORCID https://orcid.org/0000-0003-3488-6594
Peter A BealDepartment of Chemistry, University of California, Davis, California, USA.ORCID https://orcid.org/0000-0003-4855-7185

Funding

Supplement: Defining and Controlling Protein-RNA interactions in editing and interference pathwaysR35GM141907 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI PETER A. BEAL · 2021 to 2026
$3.2M
Supplement:High-throughput screening and structure-guided optimization of oligonucleotides for site-directed RNA editing by ADARsR01GM149799 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI ANDREW J FISHER · 2023 to 2026
$1.4M
NIGMS NIH HHS R01 GM149799NIGMS NIH HHS R35 GM141907NIH HHS R35GM141907
6 · The paper itself

Abstract

Oligonucleotides capable of guiding adenosine deaminases acting on RNA (ADARs) to carry out therapeutic adenosine (A) to inosine (I) editing constitute a promising new class of nucleic acid therapeutics. However, our understanding of the impact of different chemical modifications at the various nucleotide positions in ADAR guide strands is limited. While ribose 2' modification is common in ADAR-directing guides, less is known about the impact of modification at the 4' position. Here we describe the synthesis of several 4'-Cα-methyl and 2'-O, 4'-Cα-dimethyl derivatives of adenosine, uridine, and cytidine and their incorporation into RNA. In addition, we show that these analogs maintain the base pairing selectivity of their parent nucleoside and modulate duplex thermal stability in an analog-dependent manner. High-resolution crystal structures of RNA duplexes bearing 4'-Cα-methyl A or U showed that these analogs adopt a C3'-endo sugar pucker and project 4' substituents into the minor groove. Finally, we find that 2'-O, 4'-Cα-dimethyluridine and 2'-O, 4'-Cα-dimethyladenosine strategically positioned in ADAR guide strands can increase the selectivity of the editing reaction for target sequences with adjacent off-target adenosines. This work advances our understanding of the ADAR reaction mechanism and informs the design of ADAR guide strands with improved selectivity.

Indexed as

Adenosine DeaminaseRibonucleosidesRNAAdenosineBase PairingCrystallography, X-RayCytidineHumansInosineNucleic Acid ConformationRNA EditingUridineAdenosineAdenosine DeaminaseCytidineInosineRibonucleosidesRNAUridine

Identifiers

PMID41318945
PMCPMC13195036

What OpenQuestion holds

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Registered trials

None linked

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.