A cytosine analogue containing a conformationally flexible acyclic linker for triplex formation at sites with contiguous G-C base pairs

Two nucleoside derivatives of the pyrimidine bases T and m 5ox C have been prepared with flexible acyclic carbohydrate linkers. A new procedure, beginning with ( R )-(−)-2,2-dimethyl-1,3-dioxolane-4-methanol permits the preparation of the stereochemically pure acyclic derivatives of both protected nucleoside analogues without contamination by a problematic rearrangement product. By simply increasing the flexibility of the carbohydrate portion of the am 5ox C nucleoside derivative, 15-mer triplexes containing five contiguous G-C base pairs exhibit a 7–8°C increase in T m value.