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

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 characteri...

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Autores principales:	Fika Ayu Safitri, Anh Thi Tram Tu, Kazuaki Hoshi, Miwako Shobo, Dandan Zhao, Arief Budi Witarto, Sony Heru Sumarsono, Ernawati Arifin Giri-Rachman, Kaori Tsukakoshi, Kazunori Ikebukuro, Tomohiko Yamazaki
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	guanine quadruplex high-order structure monomeric immunostimulatory activity adjuvant Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0cb9662d3dce41ee8d9804a7db7436e6
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spelling	oai:doaj.org-article:0cb9662d3dce41ee8d9804a7db7436e62021-11-25T16:52:51ZEnhancement of the Immunostimulatory Effect of Phosphodiester CpG Oligodeoxynucleotides by an Antiparallel Guanine-Quadruplex Structural Scaffold10.3390/biom111116172218-273Xhttps://doaj.org/article/0cb9662d3dce41ee8d9804a7db7436e62021-11-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1617https://doaj.org/toc/2218-273XGuanine-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′ terminal and one cytosine/adenine in the 5′ 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.Fika Ayu SafitriAnh Thi Tram TuKazuaki HoshiMiwako ShoboDandan ZhaoArief Budi WitartoSony Heru SumarsonoErnawati Arifin Giri-RachmanKaori TsukakoshiKazunori IkebukuroTomohiko YamazakiMDPI AGarticleguanine quadruplexhigh-order structuremonomericimmunostimulatory activityadjuvantMicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1617, p 1617 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	guanine quadruplex high-order structure monomeric immunostimulatory activity adjuvant Microbiology QR1-502
spellingShingle	guanine quadruplex high-order structure monomeric immunostimulatory activity adjuvant Microbiology QR1-502 Fika Ayu Safitri Anh Thi Tram Tu Kazuaki Hoshi Miwako Shobo Dandan Zhao Arief Budi Witarto Sony Heru Sumarsono Ernawati Arifin Giri-Rachman Kaori Tsukakoshi Kazunori Ikebukuro Tomohiko Yamazaki Enhancement of the Immunostimulatory Effect of Phosphodiester CpG Oligodeoxynucleotides by an Antiparallel Guanine-Quadruplex Structural Scaffold
description	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′ terminal and one cytosine/adenine in the 5′ 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.
format	article
author	Fika Ayu Safitri Anh Thi Tram Tu Kazuaki Hoshi Miwako Shobo Dandan Zhao Arief Budi Witarto Sony Heru Sumarsono Ernawati Arifin Giri-Rachman Kaori Tsukakoshi Kazunori Ikebukuro Tomohiko Yamazaki
author_facet	Fika Ayu Safitri Anh Thi Tram Tu Kazuaki Hoshi Miwako Shobo Dandan Zhao Arief Budi Witarto Sony Heru Sumarsono Ernawati Arifin Giri-Rachman Kaori Tsukakoshi Kazunori Ikebukuro Tomohiko Yamazaki
author_sort	Fika Ayu Safitri
title	Enhancement of the Immunostimulatory Effect of Phosphodiester CpG Oligodeoxynucleotides by an Antiparallel Guanine-Quadruplex Structural Scaffold
title_short	Enhancement of the Immunostimulatory Effect of Phosphodiester CpG Oligodeoxynucleotides by an Antiparallel Guanine-Quadruplex Structural Scaffold
title_full	Enhancement of the Immunostimulatory Effect of Phosphodiester CpG Oligodeoxynucleotides by an Antiparallel Guanine-Quadruplex Structural Scaffold
title_fullStr	Enhancement of the Immunostimulatory Effect of Phosphodiester CpG Oligodeoxynucleotides by an Antiparallel Guanine-Quadruplex Structural Scaffold
title_full_unstemmed	Enhancement of the Immunostimulatory Effect of Phosphodiester CpG Oligodeoxynucleotides by an Antiparallel Guanine-Quadruplex Structural Scaffold
title_sort	enhancement of the immunostimulatory effect of phosphodiester cpg oligodeoxynucleotides by an antiparallel guanine-quadruplex structural scaffold
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0cb9662d3dce41ee8d9804a7db7436e6
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Enhancement of the Immunostimulatory Effect of Phosphodiester CpG Oligodeoxynucleotides by an Antiparallel Guanine-Quadruplex Structural Scaffold

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