The potential of N2-modified cap analogues for precise genetic manipulation through mRNA engineering.

Autor:	Kurpiejewski K; Faculty of Chemistry, University of Warsaw, Warsaw, Poland., Stankiewicz-Drogon A; Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Warsaw, Poland., Piecyk K; Faculty of Chemistry, University of Warsaw, Warsaw, Poland., Rajkowska E; Faculty of Chemistry, University of Warsaw, Warsaw, Poland., Skrzypczyk P; Faculty of Chemistry, University of Warsaw, Warsaw, Poland., Geng J; Centre of New Technologies, University of Warsaw, Warsaw, Poland., Darzynkiewicz E; Centre of New Technologies, University of Warsaw, Warsaw, Poland., Grzela R; Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Warsaw, Poland., Jankowska-Anyszka M; Faculty of Chemistry, University of Warsaw, Warsaw, Poland.
Jazyk:	angličtina
Zdroj:	Frontiers in molecular biosciences [Front Mol Biosci] 2024 Feb 06; Vol. 10, pp. 1269028. Date of Electronic Publication: 2024 Feb 06 (Print Publication: 2023).
DOI:	10.3389/fmolb.2023.1269028
Abstrakt:	The technology of mRNA-based drugs is currently being intensively developed and implemented. Medical products of this type are already being used as viral vaccines and could potentially find application in a wide range of diseases. The tremendous interest in mRNA is due to the relatively easy production process, which can be quickly adapted to meet societal needs. The properties of this molecule depend on the structure of its individual components, such as the structure of the cap at the 5' end. Modifications of the cap significantly affect the translational potential and lifespan of the whole mRNA. In the current work, we present the synthesis of derivatives of cap analogues modified at the N2 position of 7-methylguanosine. In addition to the substituent at the N2 position, the derivatives had either an extended triphosphate chain, a thiophosphate modification, an added cap1-modified nucleotide or an extended linker between the substituent and 7-methylguanosine. The compounds were tested for use as translation inhibitors and as components for mRNA preparation and appeared of interest for both applications. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Kurpiejewski, Stankiewicz-Drogon, Piecyk, Rajkowska, Skrzypczyk, Geng, Darzynkiewicz, Grzela and Jankowska-Anyszka.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu