Triplex Formation with α-L-LNA (α-L-Ribo-Configured Locked Nucleic Acid)

摘要

The specific recognition of homopurine—homopyrimidine tracts in duplex DNA by triplex-forming oligonucleotides (TFOs) provides an attractive strategy for genetic manipulation and is therefore of interest in medicinal chemistry and biotechnology. In a triplex, the TFO is located in the major groove of a DNA duplex where it interacts with the purines in the duplex through Hoogsteen hydrogen bonding. In the parallel TFO binding motif, T:A·T and C:G·C~+ base triplets are formed. However, formation of C:G·C~+ base triplets is pH dependent and disfavored at physiological pH, and thus, targeting of mixed G and A sequences becomes unfeasible at physiological pH. Despite considerable efforts over the past decade, the instability of pyrimidine motif triplexes at physiological pH continues to limit the biological applications.