A versatile post-synthetic method on a solid support for the synthesis of RNA containing reduction-responsive modifications

Abstract

An original post-synthetic method on a solid support was developed to introduce various disulfide bond containing groups at the 2′-OH of oligoribonucleotides (RNAs). It is based on a thiol disulfide exchange reaction between several readily accessible alkyldisulfanyl-pyridine derivatives and 2′-O-acetylthiomethyl RNA in the presence of butylamine. By this strategy, diverse 2′-O-alkyldithiomethyl RNAs were obtained. These modifications provided high nuclease resistance to RNA and were easily removed with glutathione treatment, thus featuring a potential use for siRNA prodrugs.