Accessible 5 '-end of CpG-containing phosphorothioate oligodeoxynucleotides is essential for immunostimulatory activity

In our ongoing efforts to decipher the sequence and structural requirements in the flanking region of the CpG motif in phosphorothioate oligodeoxynucl eotides (PS-oligos), we have examined the requirement of free 5'- and 3'-en ds of PS-oligos on immune stimulation. Our model studies using 3'-3'-linked (containing two free 5'-ends) and 5'-5'-linked (containing two free 3'-end s) CpG-containing PS-oligos demonstrate that immunostimulatory activity is significantly reduced when the 5'-end of the PS-oligo is not accessible, ra ther than the 3'-end, suggesting that the 5'-end plays a critical role in i mmunostimulatory activity. (C) 2000 Elsevier Science Ltd. All rights reserv ed.