N1-Methylpseudouridine

N1-Methylpseudouridine (abbreviated m1Ψ) is a natural tRNA component[1] as well as a synthetic pyrimidine nucleoside used in biochemistry and molecular biology for in vitro transcription and is found in the SARS-CoV-2 mRNA vaccines tozinameran (Pfizer–BioNTech) and elasomeran (Moderna).

N1-Methylpseudouridine
Names
IUPAC name
5-[(2S,3R,4S,5R)-3,4-Dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1-methylpyrimidine-2,4-dione
Other names
1-Methylpseudouridine; m1Ψ
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
UNII
  • InChI=1S/C10H14N2O6/c1-12-2-4(9(16)11-10(12)17)8-7(15)6(14)5(3-13)18-8/h2,5-8,13-15H,3H2,1H3,(H,11,16,17)/t5-,6-,7-,8+/m1/s1
    Key: UVBYMVOUBXYSFV-XUTVFYLZSA-N
  • O[C@H]1[C@@](O[C@H](CO)[C@H]1O)(C=2C(=O)NC(=O)N(C)C2)[H]
Properties
C10H14N2O6
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Properties

N1-Methylpseudouridine is the methylated derivative of pseudouridine. It is used in in vitro transcription and for the production of RNA vaccines,[2][3] In vertebrates, it stimulates significantly less activation of the innate immune response compared to uridine.[4] At the same time, the translation is stronger.[5][6] In protein biosynthesis, it is read like uridine and enables comparatively high protein yields.[6][7] In 2016, a protocol for large-scale synthesis of the nucleoside triphosphate from the ribonucleoside was published.[8] The nucleoside itself can be made by chemical methylation of pseudouridine.[9]

References
  1. Jan Philip Wurm, Marco Griese, Ute Bahr, Martin Held, Alexander Heckel, Michael Karas, Jörg Soppa, Jens Wöhnert (Mar 2012). "Identification of the enzyme responsible for N1-methylation of pseudouridine 54 in archaeal tRNAs". RNA. 18 (3): 412–420. doi:10.1261/rna.028498.111. PMC 3285930. PMID 22274954.CS1 maint: multiple names: authors list (link)
  2. Knudson CJ, Alves-Peixoto P, Muramatsu H, Stotesbury C, Tang L, Lin PJ, et al. (May 2021). "Lipid-nanoparticle-encapsulated mRNA vaccines induce protective memory CD8 T cells against a lethal viral infection". Molecular Therapy. doi:10.1016/j.ymthe.2021.05.011. PMID 33992803.
  3. Krienke C, Kolb L, Diken E, Streuber M, Kirchhoff S, Bukur T, et al. (January 2021). "A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis". Science. 371 (6525): 145–153. Bibcode:2021Sci...371..145K. doi:10.1126/science.aay3638. PMID 33414215. S2CID 231138578.
  4. Nelson J, Sorensen EW, Mintri S, Rabideau AE, Zheng W, Besin G, et al. (June 2020). "Impact of mRNA chemistry and manufacturing process on innate immune activation". Science Advances. 6 (26): eaaz6893. Bibcode:2020SciA....6.6893N. doi:10.1126/sciadv.aaz6893. PMC 7314518. PMID 32637598.
  5. Andries O, Mc Cafferty S, De Smedt SC, Weiss R, Sanders NN, Kitada T (November 2015). "N(1)-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice". Journal of Controlled Release. 217: 337–44. doi:10.1016/j.jconrel.2015.08.051. hdl:1854/LU-6993270. PMID 26342664.
  6. Svitkin YV, Cheng YM, Chakraborty T, Presnyak V, John M, Sonenberg N (June 2017). "N1-methyl-pseudouridine in mRNA enhances translation through eIF2α-dependent and independent mechanisms by increasing ribosome density". Nucleic Acids Research. 45 (10): 6023–6036. doi:10.1093/nar/gkx135. PMC 5449617. PMID 28334758.
  7. Parr CJ, Wada S, Kotake K, Kameda S, Matsuura S, Sakashita S, et al. (April 2020). "N 1-Methylpseudouridine substitution enhances the performance of synthetic mRNA switches in cells". Nucleic Acids Research. 48 (6): e35. doi:10.1093/nar/gkaa070. PMC 7102939. PMID 32090264.
  8. Shanmugasundaram M, Senthilvelan A, Kore AR (December 2016). "Gram-Scale Chemical Synthesis of Base-Modified Ribonucleoside-5'-O-Triphosphates". Current Protocols in Nucleic Acid Chemistry. 67: 13.15.1–13.15.10. doi:10.1002/cpnc.20. PMID 27911496. S2CID 5143935.
  9. Robert A. Earl, Leroy B. Townsend (Jun 1977). "A chemical synthesis of the nucleoside 1-methylpseudouridine". Journal of Heterocyclic Chemistry.
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