PMID: 11310616Apr 20, 2001Paper

Effect of chemical modifications of cytosine and guanine in a CpG-motif of oligonucleotides: structure-immunostimulatory activity relationships

Bioorganic & Medicinal Chemistry
E R KandimallaS Agrawal

Abstract

Oligodeoxynucleotides containing unmethylated CpG-motifs stimulate the innate immune system, including inducing B-cell proliferation and cytokine production. However, the mechanism of immunostimulation by CpG-oligonucleotides and the precise structural requirements and specific functional groups of cytosine and guanine necessary for recognition of and interaction with protein/receptor factors that are responsible for immune stimulation have not been elucidated. We sought to understand the critical role of each functional group of the cytosine and guanine moieties in a CpG-motif in inducing immunostimulatory activity. To this end, we examined structure-immunostimulatory activity relationships of phosphorothioate oligodeoxynucleotides (PS-oligos) containing YpG- and CpR-motifs (Y and R stand for pyrimidine and purine analogues, respectively). The PS-oligos containing a YpG-motif in which the natural deoxycytidine was replaced with deoxy-5-hydroxycytidine or deoxy-N4-ethylcytidine showed immunostimulatory activity. Substitution of deoxycytidine with a deoxy-5-methylisocytidine, deoxyuridine, or deoxy-P-base-nucleoside in the YpG-motif completely abolished the immunostimulatory activity, similar to the results observed with deoxy-5...Continue Reading

References

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Citations

Feb 1, 2003·Biochemical and Biophysical Research Communications·Lakshmi BhagatSudhir Agrawal
May 22, 2003·Biochimica Et Biophysica Acta·Takeshi ShimosatoTadao Saito
Mar 7, 2002·Trends in Molecular Medicine·Sudhir Agrawal, Ekambar R Kandimalla
Jun 27, 2006·Nucleic Acids Research·Mallikarjuna Reddy PuttaSudhir Agrawal
Jul 14, 2010·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Gaurav K Gupta, Devendra K Agrawal
Apr 30, 2005·Proceedings of the National Academy of Sciences of the United States of America·Ekambar R KandimallaSudhir Agrawal
Nov 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·Ekambar R KandimallaSudhir Agrawal
Jun 7, 2005·Expert Opinion on Biological Therapy·Jörg Vollmer
Oct 3, 2009·Annals of the New York Academy of Sciences·Denise Richardt-Pargmann, Jörg Vollmer
Jan 31, 2004·Annals of the New York Academy of Sciences·Sudhir Agrawal, Ekambar R Kandimalla
Apr 13, 2010·Cellular Immunology·Mary StruthersDanilo R Casimiro
Aug 28, 2004·Cellular Immunology·Weiwen JiangDavid S Pisetsky
Jun 9, 2004·International Immunopharmacology·Fu-Gang ZhuSudhir Agrawal
Oct 16, 2003·Biochemical and Biophysical Research Communications·Yan-Ping CongSudhir Agrawal
Apr 28, 2004·Biochemical and Biophysical Research Communications·Weiwen JiangDavid S Pisetsky
Sep 11, 2002·Biochemical and Biophysical Research Communications·Dong YuSudhir Agrawal
Jul 5, 2006·International Reviews of Immunology·Jörg Vollmer
Jun 9, 2004·The Journal of Biological Chemistry·Christina C N WuDennis A Carson
Jun 26, 2004·Journal of Leukocyte Biology·Jörg VollmerArthur M Krieg
Jul 15, 2015·Laboratory animal research·Susan Prattis, Abdo Jurjus
Apr 23, 2008·Current Protocols in Nucleic Acid Chemistry·Ekambar R Kandimalla, Sudhir Agrawal
Nov 23, 2007·Biochemical Society Transactions·S Agrawal, E R Kandimalla
Apr 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jehad H EdwanDevendra K Agrawal
Mar 10, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jitka StankovaRima Rozen
Aug 24, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Maria V NesterovaYoon S Cho-Chung
Apr 7, 2010·Journal of Medicinal Chemistry·Mallikarjuna Reddy PuttaEkambar R Kandimalla
Nov 9, 2007·Journal of Medicinal Chemistry·Dong YuSudhir Agrawal
Feb 14, 2013·ACS Medicinal Chemistry Letters·Mallikarjuna R PuttaSudhir Agrawal
Oct 31, 2003·Journal of Medicinal Chemistry·Sukunath NarayananClemens Richert

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