Immunostimulatory properties of phosphorothioate CpG DNA containing both 3'-5'- and 2'-5'-internucleotide linkages

Nucleic Acids Research
Dong YuSudhir Agrawal

Abstract

Synthetic oligodeoxyribonucleotides containing CpG-dinucleotides (CpG DNA) in specific sequence contexts activate the vertebrate immune system. We have examined the effect of 3'-deoxy-2'-5'-ribonucleoside (3'-deoxynucleoside) incorporation into CpG DNA on the immunostimulatory activity. Incorporation of 3'-deoxynucleosides results in the formation of 2'-5'-internucleotide linkages in an otherwise 3'-5'-linked CpG DNA. In studies, both in vitro and in vivo, CpG DNA containing unnatural 3'-deoxynucleoside either within the CpG-dinucleotide or adjacent to the CpG-dinucleotide failed to induce immunostimulatory activity, suggesting that the modification was not recognized by the receptors. Incorporation of the same modification distal to the CpG-dinucleotide in the 5'-flanking sequence potentiated the immunostimulatory activity of the CpG DNA. The same modification when incorporated in the 3'-flanking sequence had an insignificant effect on immunostimulatory activity of CpG DNA. Interestingly, substitution of a 3'-deoxynucleoside in the 5'-flanking sequence distal to the CpG-dinucleotide resulted in increased IL-6 and IL-10 secretion with similar levels of IL-12 compared with parent CpG DNA. The incorporation of the same modificati...Continue Reading

References

Apr 6, 1995·Nature·A M KriegD M Klinman
May 25, 1993·Biochemical Pharmacology·R F BrandaG Zon
Dec 2, 1998·Journal of Biomolecular Structure & Dynamics·B J Premraj, N Yathindra
Jan 5, 1999·Bioorganic & Medicinal Chemistry Letters·E R KandimallaS Agrawal
Feb 1, 2000·Molecular Medicine Today·S Agrawal, E R Kandimalla
Dec 29, 2000·Nature·H HemmiS Akira
May 9, 2001·Biochemical and Biophysical Research Communications·B J PremrajN Yathindra
Jul 27, 2001·Proceedings of the National Academy of Sciences of the United States of America·S BauerG B Lipford
Jul 27, 2001·Current Medicinal Chemistry·S A AdahP F Torrence
Aug 22, 2002·Current Cancer Drug Targets·S Agrawal, E R Kandimalla

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Citations

Feb 1, 2003·Biochemical and Biophysical Research Communications·Lakshmi BhagatSudhir Agrawal
Jun 27, 2006·Nucleic Acids Research·Mallikarjuna Reddy PuttaSudhir Agrawal
Apr 30, 2005·Proceedings of the National Academy of Sciences of the United States of America·Ekambar R KandimallaSudhir Agrawal
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
Sep 11, 2002·Biochemical and Biophysical Research Communications·Dong YuSudhir Agrawal
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, 2010·Journal of Medicinal Chemistry·Mallikarjuna Reddy PuttaEkambar R Kandimalla
Nov 9, 2007·Journal of Medicinal Chemistry·Dong YuSudhir Agrawal
Dec 24, 2008·Journal of Medicinal Chemistry·Daqing WangSudhir Agrawal
Feb 14, 2013·ACS Medicinal Chemistry Letters·Mallikarjuna R PuttaSudhir Agrawal

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