Application of Phosphoramidate ProTide Technology for the Synthesis of 5'-mRNA Cap Analogs Modified on the Exocyclic Amine Group.

Autor: Siekierska I; Faculty of Chemistry, University of Warsaw, 1 Pasteur St., 02-093, Warsaw, Poland., Lukaszewicz M; Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, 02-089, Warsaw, Poland., Worch R; Nencki Institute of Experimental Biology, 3 Pasteur Street, 02-093, Warsaw, Poland., Jankowska-Anyszka M; Faculty of Chemistry, University of Warsaw, 1 Pasteur St., 02-093, Warsaw, Poland., Piecyk K; Faculty of Chemistry, University of Warsaw, 1 Pasteur St., 02-093, Warsaw, Poland.
Jazyk: angličtina
Zdroj: ChemMedChem [ChemMedChem] 2023 Feb 14; Vol. 18 (4), pp. e202200490. Date of Electronic Publication: 2023 Jan 19.
DOI: 10.1002/cmdc.202200490
Abstrakt: Aryloxy triester phosphoramidate methodology, commonly known as ProTide technology, is one of the most widely used prodrug approaches applied to therapeutic nucleosides. This approach has been used extensively by the pharmaceutical industry and researchers in medicinal chemistry. Herein we report our adaptation of this effective method for the synthesis of bioactive 5'-mRNA cap analogues as inhibitors for targeting cap-dependent translation. The synthesis was performed in two main stages: preparation of N2-modified guanosine analogues and their subsequent transformation into prodrugs using phenylethoxy-l-alaninyl phosphorochloridate. The prepared pro-nucleotide cap analogues were tested for their capacity in enzymatic activation, inhibitory properties in a rabbit reticulocyte lysate system, and passive membrane translocation properties.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
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