Synthesis of 8-Oxo-2’-Ome-Guanosine for future aptamer modification 

Presenter(s)

Shawn Schowe

Abstract or Description

Guanosine methylated at the 2’-O position of the ribose sugar has been shown to add stability when incorporated into an RNA biopolymer. The methylation helps the biopolymer form intramolecular interactions via de-solvation. In an effort to enhance the stability of future oxidation-modified oligomers, a novel multistep synthesis for 8-oxo-guanosine methylated at the 2’ position has been developed and is currently under investigation. Difficulty with guanosine in synthesis has to do with guanosine possessing multiple reactive centers. The only way to avoid this synthetic hurdle is through the protection of these groups in a selective manner. Recently, the methylated adduct, protected at all reactive centers, has been synthesized and isolated. All structural confirmation thus far has been given via analysis of proton nuclear magnetic resonance spectroscopy. In the future, the hope is to remove the protecting groups, oxidize position 8, install a di-methoxy trital at the 5’ position, and a phosphonamidite at the 3’ position. Once accomplished, the aforementioned 8-oxo-guanosine adduct will be incorporated into an aptamer via solid phase synthesis to measure how oxidation changes the aptamers behavior.