1-methylpseudouridine
Synonym(s):N1-Methylpseudouridine;1-Methyl-5-β-D -ribofuranosyl-2,4(1H,3H)-pyrimidinedione
- CAS NO.:13860-38-3
- Empirical Formula: C10H14N2O6
- Molecular Weight: 258.229
- MDL number: MFCD10687017
- SAFETY DATA SHEET (SDS)
- Update Date: 2024-10-28 16:48:35
What is 1-methylpseudouridine?
Description
N1-Methylpseudouridine is a modified nucleoside used for enhancing mRNA translation. Incorporation of N1-Methylpseudouridine into mRNA turns off the immune/eIF2α phosphorylation-dependent inhibition of translation, and increases ribosome pausing and density on the mRNA, thus dramatically facilitating the translation process. N1-Methylpseudouridine outperforms several other modified nucleosides (e.g. 5-Methylcytidine) and corresponding combinations in terms of translation capacity.
Definition
ChEBI: 1-methylpseudouridine is a methylpseudouridine in which the methyl group is located at position N-1 on the uracil ring.
What are the applications of Application
1-Methylpseudouridine is a substitute for uridine in modified mRNA. This substitution has shown to increase transfection by reducing immuogenicity. The 1-methylpseudouridine substituted mRNA increases protein expression due to low immune stimulation as it evades detection by the edosomal Toll-like receptor (TLR3).
Biochem/physiol Actions
N1-methylpseudouridine (m1Ψ), the modification used in the current mRNA SARS-CoV-2 vaccines, was found to possess superior characteristics to Ψ; m1Ψ elicited less immunogenicity and increased protein production by more than an order of magnitude relative to Ψ m1Ψ preserves the fidelity of tRNA selection by the ribosome. Kim et al. explored the effect of m1Ψ and Ψ on decoding using various in vitro systems. They found that m1Ψ slightly decreases the rate of peptide-bond formation. It also suppresses near-stop codon recognition by release factors and m1Ψ-modified SARS-CoV-2 spike protein mRNA is translated faithfully by eukaryotic ribosomes. Unlike Ψ, m1Ψ does not stabilize mismatches during RNA-duplex formation. Ψ, but not m1Ψ, increases errors by reverse transcriptases[3].
References
1. Svitkin YV, Cheng YM, Chakraborty T, et al. N1-methyl-pseudouridine in mRNA enhances translation through eIF2α-dependent and independent mechanisms by increasing ribosome density. Nucleic Acids Research, 2017, 45(10): 6023-6036.
2. Andries O, Mc Cafferty S, De Smedt SC, et al 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, 2015, 217: 337-344.
3. Kyusik Q Kim. “N1-methylpseudouridine found within COVID-19 mRNA vaccines produces faithful protein products.” Cell reports 40 9 (2022): 111300.
Properties of 1-methylpseudouridine
Density | 1.576±0.06 g/cm3(Predicted) |
storage temp. | Store at -20°C |
solubility | >20 mg/mL in EtOH; >20.65 mg/mL in DMSO |
pka | 9.43±0.10(Predicted) |
form | A solid |
color | White to off-white |
Water Solubility | insoluble in Water; |
InChI | InChI=1/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+/s3 |
Safety information for 1-methylpseudouridine
Signal word | Warning |
Pictogram(s) |
Exclamation Mark Irritant GHS07 |
GHS Hazard Statements |
H302:Acute toxicity,oral H315:Skin corrosion/irritation H319:Serious eye damage/eye irritation H335:Specific target organ toxicity, single exposure;Respiratory tract irritation |
Precautionary Statement Codes |
P261:Avoid breathing dust/fume/gas/mist/vapours/spray. P280:Wear protective gloves/protective clothing/eye protection/face protection. P301+P312:IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. P302+P352:IF ON SKIN: wash with plenty of soap and water. P305+P351+P338:IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing. |
Computed Descriptors for 1-methylpseudouridine
InChIKey | UVBYMVOUBXYSFV-CAYFCZNJNA-N |
SMILES | [C@@H]1(O)[C@@H](CO)O[C@@H](C2C(=O)NC(=O)N(C)C=2)[C@@H]1O |&1:0,2,6,16,r| |
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