Poster abstracts
Poster number 113 submitted by Kylie Raasch
Large-scale synthesis of pseudouridine using an immobilized enzyme
Kylie Raasch (Department of Chemistry, Southern Illinois University Edwardsville), Tristan Sanford (Department of Chemistry, Southern Illinois University Edwardsville), Andrew Riley (Department of Chemistry, Southern Illinois University Edwardsville), Melanie Clawson (Department of Biological Sciences, Southern Illinois University Edwardsville), Mina Sumita (Department of Chemistry, Southern Illinois University Edwardsville)
Abstract:
Modifications of RNA molecules have a significant effect on their structure and function. One of the most common modifications is pseudoruidine (&Psi) which isomerizes from uridine. Recently, pseudouridine is in high demand due to the COVID-19 pandemic because a derivative of pseudouridine (N1-methylpseudouridine) has been used for the development of mRNA vaccines against SARS-CoV-2. However, organic synthesis of pseudouridine has been challenging because of the stereochemistry requirement and the sensitivity of reaction steps to moisture. We recently developed the three-step semi-enzymatic synthetic route for the pseudouridine synthesis using adenosine 5'-monophosphate (AMP) and uracil as the starting materials and a reverse reaction catalyzed by the pseudouiridne monophosphate glycosidase with a 68.4% overall yield. In this project, we focused on the development of a scale-up pseudouridine monophosphate production with an immobilized enzyme. This will be an environmentally friendly synthesis of pseudouridine for the production of future mRNA-based drugs.
Keywords: RNA modification, modified nucleotide synthesis, pseudouridine