Stabilisation of a nucleic acid three-way junction by an oligonucleotide containing a single 2′-C to 3′-O-phosphate butylene linkage prepared by a tandem RCM-hydrogenation method

Abstract

A cyclic dinucleotide with a butylene linker between the upper 2′-C position and the 3′-O-phosphate linkage was synthesised from simple nucleoside building blocks via a tandem ring-closing metathesis and hydrogenation procedure. The major of two phosphorus epimers was incorporated into an oligodeoxynucleotide, as well as into an LNA–DNA mixmer oligonucleotide. These were evaluated as parts in three different secondary structures, a duplex, a bulged duplex and a three-way junction, with both DNA and RNA complements. In the DNA : RNA hybrid molecule, the oligodeoxynucleotide containing this single 2′-C to 3′-O-phosphate butylene linkage was found to stabilise a three-way junction.