Immunostimulatory activity of CpG containing phosphorothioate oligodeoxynucleotide is modulated by modification of a single deoxynucleoside

Phosphorothioate oligodeoxynucleotides (PS-oligos) containing the CpG motif have immunostimulatory properties. Our earlier study had shown that the im munostimulatory activity of PS-oligos containing the CpG motif can be modul ated by incorporation of 2'-O-methylribonucleosides (Zhao, Q.; Yu, D.; Agra wal, S. Bioorg. Med. Chem. Lett. 1999, 9, 3453). Here we show that the immu nostimulatory activity of a PS-oligo containing a CpG motif can be modulate d by substitution of a single deoxynucleoside at specific sites with either 2'-O-methylribonucleoside or 3'-O-methylribonucleoside in the flanking reg ion to CpG motif. Furthermore, substitution of deoxynucleosides with 2'-O-m ethoxyethoxyribonucleosides also results in modulating immunostimulatory ac tivity of PS-oligos. (C) 2000 Elsevier Science Ltd. All rights reserved.