Directed Crosslinking of RNA by Glutathione-Triggered PNA-Quinone-Methide-Conjugates

Quinone methide precursors protected with alkyldithiomethyl groups have been synthesized and converted into PNA conjugates. Stable in the absence of reducing agents, the electrophilic quinone methide is released by glutathione in concentrations typical for the cytosol. Self-alkylation then occurs or crosslinking of RNA when hybridized with complementary strands. Fastest reactions are seen for the sterically least hindered compound.

Automated summary

Quinone methide precursors protected with alkyldithiomethyl groups have been synthesized and converted into PNA conjugates. These conjugates remain stable without reducing agents, but release electrophilic quinone methide in the presence of glutathione, typical of cytosolic concentrations. Self-alkylation or crosslinking of RNA occurs when hybridized with complementary strands, with the fastest reactions observed for the least hindered compound.