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RNA oligomers at atomic resolution containing 1‐methylpseudouridine, an essential building block of mRNA vaccines


Nievergelt, Philipp; Berliat, Florian; McAuley, Katherine E; Dorgan, Colin R; van Well, Renate Maria; Thorn, Andrea; Spingler, Bernhard (2024). RNA oligomers at atomic resolution containing 1‐methylpseudouridine, an essential building block of mRNA vaccines. ChemMedChem, 19(7):e202300600.

Abstract

All widely used mRNA vaccines against COVID‐19 contain in their sequence 1‐methylpseudouridine (m1Ψ) instead of uridine. In this publication, we report two high resolution crystal structures (at up to 1.01 and 1.32 Å, respectively) of one such double‐stranded 12‐mer RNA sequence crystallized in two crystal forms. The structures are compared with similar structures which do not contain this modification. Additionally, the X‐ray structure of 1‐methyl‐pseudouridine itself was determined.

Abstract

All widely used mRNA vaccines against COVID‐19 contain in their sequence 1‐methylpseudouridine (m1Ψ) instead of uridine. In this publication, we report two high resolution crystal structures (at up to 1.01 and 1.32 Å, respectively) of one such double‐stranded 12‐mer RNA sequence crystallized in two crystal forms. The structures are compared with similar structures which do not contain this modification. Additionally, the X‐ray structure of 1‐methyl‐pseudouridine itself was determined.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Scopus Subject Areas:Life Sciences > Biochemistry
Life Sciences > Molecular Medicine
Life Sciences > Pharmacology
Life Sciences > Drug Discovery
Life Sciences > General Pharmacology, Toxicology and Pharmaceutics
Physical Sciences > Organic Chemistry
Uncontrolled Keywords:Organic Chemistry, General Pharmacology, Toxicology and Pharmaceutics, Molecular Medicine, Drug Discovery, Biochemistry, Pharmacology
Language:English
Date:2 April 2024
Deposited On:26 Apr 2024 09:30
Last Modified:30 Jun 2024 01:41
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:1860-7179
OA Status:Hybrid
Publisher DOI:https://doi.org/10.1002/cmdc.202300600
PubMed ID:38235959
Project Information:
  • : FunderUniversität Zürich
  • : Grant ID
  • : Project Title
  • : FunderSchweizerischer Nationalfonds
  • : Grant ID206021_164018
  • : Project Title
  • : FunderGerman Federal Ministry of Education and Research
  • : Grant ID05K19WWA
  • : Project Title
  • : FunderGerman Federal Ministry of Education and Research
  • : Grant ID05K22GU5
  • : Project Title
  • : FunderDeutsche Forschungsgemeinschaft
  • : Grant IDTH2135/2-1
  • : Project Title
  • Content: Published Version
  • Language: English
  • Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)