Nucleotides: Part LII. Synthesis and biological activity of new base- modified (2'- 5')oligoadenylate trimers

Article abstract of DOI:10.1002/hlca.19970800404

Some new (2'- 5')oligoadenylate trimers, i.e., 22-28 containing the antiviral nucleoside ribavirin (= 1-(β-D-ribofuranosyl)-1H-1,2,4-triazole- 3-carboxamide; 7) and the synthetic cytokine 6-(benzylamino)purine riboside (= N⁶-benzyladenosine; 1) in different positions of the trimer, have been synthesized by the posphotriester method. The selectively blocked nucleosides 2-6 and 8-11 and the 2'-phosphodiesters 13 and 14, used for the oligonucleotide syntheses, were synthesized from the corresponding unprotected ribonucleosides 1 and 7, and isolated by silica-gel column chromatography. The fully deblocked trimers 22-28 were purified by ion- exchange chromatography on DEAE-Servavell 23-SS. The newly synthesized compounds were characterized by physical means. The ability of synthesized trimers to inhibit HIV-1 replication and to improve RNase L activation were investigated Some of the synthesized trimers showed also biological inhibition of HIV-1 reverse transcriptase and HIV-1-induced syncytia formation. It was shown that Ado(Bn)-containing trimers inhibited HIV-1- induced syncytia formation > 1500-fold, independently of the position of the Ado(Bn) residue in the oligomer chain.