Synthesis of Novel Cap Analogs Bearing Hydrophobic Purification Tag Toward Application for Preparation of Fully Capped Messenger RNA

Abstract

Messenger RNA (mRNA) is gaining attention as a new modality of oligonucleotide therapeutics. We have reported a new mRNA synthesis method, named the PureCap method, by in vitro transcription, which enables the production of completely capped mRNA. For this purpose, we designed and synthesized new cap analogs bearing hydrophobic o-nitrobenzyl groups, which function as purification tags for mRNA with a 5′-cap structure by reverse-phase high-performance liquid chromatography. In this paper, we describe the synthesis of new cap analogs, named PureCap analogs, and its application for completely capped mRNA synthesis.

Graphical Abstract