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 oligodeoxynucleotides (PS-oligos), we have examined the requirement of free 5′- and 3′-ends of PS-oligos on immune stimulation. Our model studies using 3′–3′-linked...

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Bibliographic Details
Published inBioorganic & medicinal chemistry letters Vol. 10; no. 23; pp. 2585 - 2588
Main Authors Yu, Dong, Zhao, Qiuyan, Kandimalla, Ekambar R, Agrawal, Sudhir
Format Journal Article
LanguageEnglish
Published Oxford Elsevier Ltd 04.12.2000
Elsevier
Subjects
Adjuvants, Immunologic - chemical synthesis
Adjuvants, Immunologic - chemistry
Adjuvants, Immunologic - pharmacology
Animals
Base Sequence
Biological and medical sciences
Cell Division - drug effects
CpG Islands
Immunomodulators
Lymphocytes - cytology
Lymphocytes - drug effects
Medical sciences
Mice
Mice, Inbred BALB C
Organophosphorus Compounds - chemistry
Pharmacology. Drug treatments
Spleen - cytology
Spleen - drug effects
Splenomegaly - chemically induced
Thionucleotides - chemical synthesis
Thionucleotides - chemistry
Thionucleotides - pharmacology
Cell proliferation
Spleen
Splenomegaly
Automation
Intraperitoneal administration
Rodentia
Organic phosphoramidite
Organic thiophosphate
Antisense oligonucleotide
In vitro
Immunomodulator
In vivo
Vertebrata
Immunostimulant agent
Mammalia
Structure activity relation
Mouse
Animal
Antisense DNA
Solid phase
Oligodeoxyribonucleotide
Chemical synthesis
Lymphocyte
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Summary:In our ongoing efforts to decipher the sequence and structural requirements in the flanking region of the CpG motif in phosphorothioate oligodeoxynucleotides (PS-oligos), we have examined the requirement of free 5′- and 3′-ends 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′-ends) CpG-containing PS-oligos demonstrate that immunostimulatory activity is significantly reduced when the 5′-end of the PS-oligo is not accessible, rather than the 3′-end, suggesting that the 5′-end plays a critical role in immunostimulatory activity.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(00)00537-0