ArticleNucleic acids research2017
mRNA cap analogues substituted in the tetraphosphate chain with CX2: identification of O-to-CCl2 as the first bridging modification that confers resistance to decapping without impairing translation.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Thio-modification effects on mRNA translation using a PureCap-based capping method.RSC chemical biology · 2026Article
- The 5' Cap Epitranscriptome and Beyond: Natural and Engineered 5' Cap Modifications for Optimizing mRNA Therapeutics and Functional Studies.ChemMedChem · 2026Review
- Enhancing cap-independent translation of linear mRNA.Nature communications · 2025Article
- Trinucleotide cap analogs with triphosphate chain modifications: synthesis, properties, and evaluation as mRNA capping reagents.Nucleic acids research · 2024Article
- Application of Mammalian Nudix Enzymes to Capped RNA Analysis.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Adaptation of turnip mosaic virus toVirus evolution · 2024Article
- Mesenchymal stem cell engineering by ARCA analog-capped mRNA.Molecular therapy. Nucleic acids · 2023Article
- Cap analogs with a hydrophobic photocleavable tag enable facile purification of fully capped mRNA with various cap structures.Nature communications · 2023Article
- Versatile strategy using vaccinia virus-capping enzyme to synthesize functional 5' cap-modified mRNAs.Nucleic acids research · 2023Article
- Review
- mRNA-based therapeutics: powerful and versatile tools to combat diseases.Signal transduction and targeted therapy · 2022Review
- mRNA-Based Vaccines and Mode of Action.Current topics in microbiology and immunology · 2022Review
- Novel N7-Arylmethyl Substituted Dinucleotide mRNA 5' cap Analogs: Synthesis and Evaluation as Modulators of Translation.Pharmaceutics · 2021Article
- Review
- Synthetic mRNAs; Their Analogue Caps and Contribution to Disease.Diseases (Basel, Switzerland) · 2021Review
- Cellular delivery of dinucleotides by conjugation with small molecules: targeting translation initiation for anticancer applications.Chemical science · 2021Article
- Opportunities and Challenges in the Delivery of mRNA-based Vaccines.Pharmaceutics · 2020Review
- The promise of mRNA vaccines: a biotech and industrial perspective.NPJ vaccines · 2020Review
- Biomedical applications of mRNA nanomedicine.Nano research · 2018Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Analogues of the mRNA 5'-cap are useful tools for studying mRNA translation and degradation, with emerging potential applications in novel therapeutic interventions including gene therapy. We report the synthesis of novel mono- and dinucleotide cap analogues containing dihalogenmethylenebisphosphonate moiety (i.e. one of the bridging O atom substituted with CCl2 or CF2) and their properties in the context of cellular translational and decapping machineries, compared to phosphate-unmodified and previously reported CH2-substituted caps. The analogues were bound tightly to eukaryotic translation initiation factor 4E (eIF4E), with CCl2-substituted analogues having the highest affinity. When incorporated into mRNA, the CCl2-substituted dinucleotide most efficiently promoted cap-dependent translation. Moreover, the CCl2-analogues were potent inhibitors of translation in rabbit reticulocyte lysate. The crystal structure of eIF4E in complex with the CCl2-analogue revealed a significantly different ligand conformation compared to that of the unmodified cap analogue, which likely contributes to the improved binding. Both CCl2- and CF2- analogues showed lower susceptibility to hydrolysis by the decapping scavenger enzyme (DcpS) and, when incorporated into RNA, conferred stability against major cellular decapping enzyme (Dcp2) to transcripts. Furthermore, the use of difluoromethylene cap analogues was exemplified by the development of 19F NMR assays for DcpS activity and eIF4E binding.
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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.