Conformational Conversion Enhances Cellular Uptake of F Base Double-Strand-Conjugated Oligonucleotides.

Artificial bases have emerged as a useful tool to expand genetic alphabets and biomedical applications of oligonucleotides. Herein, we reported that the conformation conversion enhances cellular uptake of hydrophobic 3,5-bis(trifluoromethyl)benzene (F) base double-strand-conjugated oligonucleotides. The formation of the F base double-strand caged the hydrophobic F base in the duplex strand, thus preventing F base from interacting with cells to some extent. However, upon conversion of F base double-strand-conjugated oligonucleotide to F base single-strand-conjugated oligonucleotide, F bases then were allowed to interact with cells by stronger hydrophobic interactions, followed by cellular uptake. The results were concluded as a pairing-induced cage effect of F base and have the potential for the construction of stimuli-responsive cellular uptake of functional nucleic acids.