INTERSTRAND COMPLEX-FORMATION OF PURINE OLIGONUCLEOTIDES AND THEIR NONIONIC ANALOGS - THE MODEL SYSTEM OF D(AG)(8) AND ITS COMPLEMENT, D(CT)(8)

We have investigated the role of purines in interstrand complex format ion with regard to substitution of the negatively-charged, phosphodies ter backbone by a nonionic, internucleoside linkage. Using the purine oligomer, d(AG)(8), its methylphosphonate analog, d(<(AG)under bar>)(8 ), and the complementary pyrimidine oligomer, d(CT)(8), as a model sys tem, the stoichiometry, conformation, and stability of complexes forme d at pH 8 were studied by spectroscopic and electrophoretic methods. W hen there is only one oligomer species in solution, d(<(AG)under bar>) (8) behaves as a single-stranded molecule. In contrast, the d(<(AG)und er bar>)(8) oligomer readily forms an intermolecular self-complex, par ticularly in the presence of magnesium ion. Using either purine oligom er, duplexes can form with the d(CT)(8) strand which differ in terms o f their conformation and in the dependence of their thermal stability on sodium and magnesium ions. All studies show that a stable tripler f orms with a 1:2 d(CT)(8):d(<(AG)under bar>)(8) stoichiometry which doe s not require high concentrations of sodium or magnesium ions. Tripler formation between the d(CT)(8) strand and two d(AG)(8) strands was no t observed. Native gel electrophoresis suggests that a 1:1:1 d(CT)(8): d(AG)(8):(<(AG)under bar>)(8) complex may be formed. In regard to trip ler formation, the advantage of the methylphosphonate backbone on the purine strand is clearly demonstrated.