Design and evaluation of novel nucleoside analogs (WNA) for specific formation of non-natural type triplexes containing a TA or CG interrupting site.

In a search of suitable recognition molecules for the formation of stable non-natural triplex DNA, we have developed the new nucleoside analogs (WNA, W-shape nucleoside analog) bearing an aromatic ring, a recognition base and a bicyclic skeleton to hold them. A successful result with WNA-betaT that recognizes a TA base pair selectively has suggested that the basic structure of the WNA is useful as a scaffold for search of other candidates for the formation of triplex containing a TA or a CG interrupting site. In this study, we have synthesized and investigated binding property of a variety of WNA candidates. As a result, we have determined new potential analog, WNA-betaC for a CG interrupting site. It should be noted that the triplexes containing a WNA-betaT:TA or a WNA-betaC:CG base triplet have exhibited higher stability than the natural anti-parallel triplexes constructed of A:AT and G:GC triplets. The results that H-WNA-betaT lacking a benzene ring did not show stabilization effect to any base pairs have clearly indicated that a benzene ring plays a key role in stability of triplexes.