Synthesis of oligonucleotides containing 5′-homo-4′-selenouridine derivative and its increased resistance against nuclease

Abstract

As technologies using RNA or DNA have been developed, various chemical modifications of nucleosides have been attempted to increase the stability of oligonucleotides. Since it is known that 2′-OMe-modification greatly contributes to increasing the stability of oligonucleotides, we added 2′-OMe to our previously developed 4′-selenonucleoside and 5′-homo-4′-selenonucleoside as the modified monomers for oligonucleotide: 2′-methoxy-4′-selenouridine (2′-OMe-4′-Se-U) and 5′-homo-2′-methoxy-4′-selenouridine (5′-homo-2′-OMe-4′-Se-U). We synthesized oligonucleotides containing the chemically modified 4′-selenouridine and evaluated their thermal stability and nuclease resistance. In conclusion, the nuclease stability of the oligonucleotide containing 5′-homo-2′-OMe-4′-selenouridine increased while its thermal stability decreased. © 2023