Synthesis and monitored selection of nucleotide surrogates for binding T :A base pairs in homopurine-homopyrimidine DNA triple helices

A total of 16 oligodeoxyribonucleotides of general sequence 5 ' -TCTTCTZTGT TTCT-3 ', where Z denotes an N-acyl-N-(2-hydroxyethyl)glycine residue, were prepared via solid phase synthesis. The ability of these oligonucleotides to form triplexes with the duplex 5 ' AGAAGATAGAAAGA-HEG-TCTTTCTATCTTCT-3 ' , where HEG is a hexaethylene glycol linker, was tested. In these triplexes , an 'interrupting' T:A base pair faces the Z residue in the third strand. Among the acyl moieties of Z tested, an anthraquinone carboxylic acid resid ue linked via a glycinyl group gave the most stable triplex, whose UV melti ng point was 8.4 degreesC higher than that of the triplex with 5 ' -TCTTCTG TCTTTGT-3 ' as the third strand. The results from exploratory nuclease sele ction experiments suggest that a combinatorial search for strands capable o f recognizing mixed sequences by triple helix formation is feasible.