STABILITY AND STRUCTURE OF DNA OLIGONUCLEOTIDES CONTAINING NONSPECIFIC BASE ANALOGS

The nature of DNA containing the deoxyribosyl derivative of 5-nitroind ole has been investigated. 5-Nitroindole has been shown to give good s tability when present in duplexes opposite natural bases, with only sl ightly reduced melting temperatures. However, enhanced stability occur s when it is incorporated as an additional bulged base in duplexes. It also markedly enhances the stability of duplexes when it is present a s a pendant base at either the 5' or 3'-ends of the two strands. The s tabilisation is presumed to be due to enhanced stacking interactions f or the nitroindole base. Oligomers containing a number of consecutive 5-nitroindole residues form stable, stacked secondary structures. An o ligomer containing 21 such substitutions is presumed to exist as a hai rpin structure. This was further investigated by circular dichroism me lting experiments, which demonstrated that the single-stranded oligome r contains significant secondary structure in the region of the 5-nitr oindole tract, which appears to contain a double-stranded stem. X-ray analysis of 5-nitroindole deoxyriboside provides some indication of ho w the mode of stacking observed in crystals of the nucleoside may also be responsible for stabilising secondary structures of oligonucleotid es. (C) 1997 Academic Press Limited.