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

被引:49
作者
Zhao, QY [1 ]
Yu, D [1 ]
Agrawal, S [1 ]
机构
[1] Hybridon Inc, Milford, MA 01757 USA
关键词
D O I
10.1016/S0960-894X(00)00157-8
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Phosphorothioate oligodeoxynucleotides (PS-oligos) containing the CpG motif have immunostimulatory properties. Our earlier study had shown that the immunostimulatory activity of PS-oligos containing the CpG motif can be modulated by incorporation of 2'-O-methylribonucleosides (Zhao, Q.; Yu, D.; Agrawal, S. Bioorg. Med. Chem. Lett. 1999, 9, 3453). Here we show that the immunostimulatory activity of a PS-oligo containing a CpG motif can be modulated by substitution of a single deoxynucleoside at specific sites with either 2'-O-methylribonucleoside or 3'-O-methylribonucleoside in the flanking region to CpG motif. Furthermore, substitution of deoxynucleosides with 2'-O-methoxyethoxyribonucleosides also results in modulating immunostimulatory activity of PS-oligos. (C) 2000 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:1051 / 1054
页数:4
相关论文
共 15 条
[11]   CpG DNA as mucosal adjuvant [J].
McCluskie, MJ ;
Davis, HL .
VACCINE, 1999, 18 (3-4) :231-237
[12]   STIMULATION OF MURINE LYMPHOCYTE-PROLIFERATION BY A PHOSPHOROTHIOATE OLIGONUCLEOTIDE WITH ANTISENSE ACTIVITY FOR HERPES-SIMPLEX VIRUS [J].
PISETSKY, DS ;
REICH, CF .
LIFE SCIENCES, 1994, 54 (02) :101-107
[13]  
Zhao QY, 1999, BIOORG MED CHEM LETT, V9, P3453
[14]   Pattern and kinetics of cytokine production following administration of phosphorothioate oligonucleotides in mice [J].
Zhao, QY ;
Temsamani, J ;
Zhou, RZ ;
Agrawal, S .
ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT, 1997, 7 (05) :495-502
[15]   Effect of different chemically modified oligodeoxynucleotides on immune stimulation [J].
Zhao, QY ;
Temsamani, J ;
Iadarola, PL ;
Jiang, ZW ;
Agrawal, S .
BIOCHEMICAL PHARMACOLOGY, 1996, 51 (02) :173-182