AZOLE SUBSTITUTED OLIGONUCLEOTIDES PROMOTE ANTIPARALLEL TRIPLEX FORMATION AT NON-HOMOPURINE DUPLEX TARGETS

The ability of certain azole substituted oligodeoxyribonucleotides to promote antiparallel triple helix formation with duplex targets having CG or TA interruptions in the otherwise homopurine sequence was exami ned, 2'-Deoxyribonucleosides of the azoles, which include pyrazole, im idazole, 1,2,4-triazole and 1,2,3,4-tetrazole were synthesized using t he stereospecific sodium salt glycosylation procedure. These nucleosid es were successfully incorporated using solid-support, phosphoramidite chemistry, into oligonucleotides designed to interact with the non-ho mopurine duplex targets, The interaction of these modified oligonucleo tides with all four possible base pairs was evaluated and compared to similar data for a series of natural oligonucleotides, The oligonucleo tides containing simple azoles enhanced the tripler forming ability co nsiderably at non-homopurine targets, Binding of these modified oligon ucleotides to duplex targets containing TA inversion sites was particu larly noteworthy, and compare favorably to unmodified oligonucleotides for binding to duplex targets containing CG as well as TA base pairs, The selectivity exhibited by certain azoles is suggestive of base pai r specific interactions, Thus, the azoles evaluated during this study show considerable promise for efforts to develop generalized tripler f ormation at non-homopurine duplex sequences.