CHEMICAL SYNTHESIS AND BIOLOGICAL-ACTIVITIES OF ANALOGS OF 2',5'-OLIGOADENYLATES CONTAINING 8-SUBSTITUTED ADENOSINE DERIVATIVES

The synthesis of sequence-specific 2'-5' oligonucleotides and analogues of 2'-5' linked oligoadenylates containing 8-substituted adenosine derivatives [8-hydroxypropyladenosine (AHPr) and 8-hydroxyadenosine (A0H)] is reported. The reaction of 5'-phosphoroimidazolidate of 8-substituted adenosines under conditions of lead ion catalyst did not give the corresponding 2'-5' oligoadenylates containing pAHPr and pA0H. When these reactions were carried out in the presence of uranyl ion (UO2 2+) in place of lead ion as a catalyst, the desired 2'-5' oligoadenylates were obtained. The p5'AHPr2'p5'AHPr2'p5'AHPr and p5'AOH2'p5'AOH2'p5'AOH, p5'A2'p5'A2'pAOH were slightly resistant to snake venom phosphodiesterase. The both circular dichroism and 1H-NMR spectra studies were used to characterize the modified 2'-5 oligoadenylates. Further, the biological activity evaluations of 8-substituted analogues of 2-5A are also described. © 1990 Oxford University Press.