Enhancement of the Immunostimulatory Effect of Phosphodiester CpG Oligodeoxynucleotides by an Antiparallel Guanine-Quadruplex Structural Scaffold

Safitri, Fika Ayu; Tu, Anh Thi Tram; Hoshi, Kazuaki et al.

Biomolecules, 2021, 11(11), 1617

Permalink : https://hdl.handle.net/2115/83822

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アクセス権
metadata only access
URI
https://hdl.handle.net/2115/83822
タイトル
Enhancement of the Immunostimulatory Effect of Phosphodiester CpG Oligodeoxynucleotides by an Antiparallel Guanine-Quadruplex Structural Scaffold
著者
Safitri, Fika Ayu ; Tu, Anh Thi Tram ; Hoshi, Kazuaki ; Shobo, Miwako ; Zhao, Dandan ; Witarto, Arief Budi ; Sumarsono, Sony Heru ; Giri-Rachman, Ernawati Arifin ; Tsukakoshi, Kaori ; Ikebukuro, Kazunori ; Yamazaki, Tomohiko
著者名
Safitri, Fika Ayu
著者名
Tu, Anh Thi Tram
著者名
Hoshi, Kazuaki
著者名
Shobo, Miwako
著者名
Zhao, Dandan
著者名
Witarto, Arief Budi
著者名
Sumarsono, Sony Heru
著者名
Giri-Rachman, Ernawati Arifin
著者名
Tsukakoshi, Kaori
著者名
Ikebukuro, Kazunori
著者名
Yamazaki, Tomohiko
言語
英語
キーワード
guanine quadruplex
high-order structure
monomeric
immunostimulatory activity
adjuvant
発行日
2021-11
出版者
MDPI
収録物名
Biomolecules
巻(号)
11(11)
ページ
1617
抄録
Guanine-quadruplex-based CpG oligodeoxynucleotides (G4 CpG ODNs) have been developed as potent immunostimulatory agents with reduced sensitivity to nucleases. We designed new monomeric G4 ODNs with an antiparallel topology using antiparallel type duplex/G4 ODNs as robust scaffolds, and we characterized their topology and effects on cytokine secretion. Based on circular dichroism analysis and quantification of mRNA levels of immunostimulatory cytokines, it was found that monomeric antiparallel G4 CpG ODNs containing two CpG motifs in the first functional loop, named G2.0.0, could maintain antiparallel topology and generate a high level of immunostimulatory cytokines in RAW264 mouse macrophage-like cell lines. We also found that the flanking sequence in the CpG motif altered the immunostimulatory effects. Gc2c.0.0 and Ga2c.0.0 are monomeric antiparallel G4 CpG ODNs with one cytosine in the 3 & PRIME; terminal and one cytosine/adenine in the 5 & PRIME; terminal of CpG motifs that maintained the same resistance to degradation in serum as G2.0.0 and improved interleukin-6 production in RAW264 and bone marrow-derived macrophages. The immunostimulatory activity of antiparallel G4 CpG ODNs is superior to that of linear natural CpG ODNs. These results provide insights for the rational design of highly potent CpG ODNs using antiparallel G4 as a robust scaffold.
資源タイプ
学術雑誌論文
出版タイプ
Version of Record
関連情報 (isIdenticalTo)
出版社版DOI
https://doi.org/10.3390/biom11111617