Poster: Chemical Synthesis of 5’-capped RNA Substrates of Viral Enzymes.
This poster has received a special award at the 19 th Days of Young Researchers Society of Therapeutic Chemistry in Romainville (France).
Over the last decades, a large increase in emerging RNA viruses was noticed. Because of the lack of efficient treatments for infections, the enzymes involved in the viral mRNA processing could be potential targets for antiviral drug design. The RNA processing consists in a cap structure which is a N7- methylguanosine linked to the 5’-terminal nucleoside of the pre-mRNA via a 5’-5’ triphosphate linkage. This cap moiety (7mGppp) is an essential RNA structural modification allowing its efficient translation, limiting its degradation by cellular 5’-exonucleases and avoiding its recognition as « nonself » by the innate immunity machinery. Due to the chemical nature of N7-methylguanosine, the lack of methods allowing the synthesis of large amounts of 5’-capped RNAs have hampered biological and structural studies of proteins recognizing the cap structure or involved in the capping pathway. In the present work, we combined a chemical synthesis method on solid support and an enzymatic methylation assay in order to produce large amounts of RNA carrying different cap structures1-3 which will act as bona fine substrates mimicking cellular capped RNAs and can be used for biochemical and structural studies.
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