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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615816/ https://www.ncbi.nlm.nih.gov/pubmed/34827615 http://dx.doi.org/10.3390/biom11111617 |
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author | 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 |
author_facet | 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 |
author_sort | Safitri, Fika Ayu |
collection | PubMed |
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 | Online Article Text |
id | pubmed-8615816 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86158162021-11-26 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 Shobo, Miwako Zhao, Dandan Witarto, Arief Budi Sumarsono, Sony Heru Giri-Rachman, Ernawati Arifin Tsukakoshi, Kaori Ikebukuro, Kazunori Yamazaki, Tomohiko Biomolecules Article 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. MDPI 2021-11-01 /pmc/articles/PMC8615816/ /pubmed/34827615 http://dx.doi.org/10.3390/biom11111617 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article 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 Enhancement of the Immunostimulatory Effect of Phosphodiester CpG Oligodeoxynucleotides by an Antiparallel Guanine-Quadruplex Structural Scaffold |
title | 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_short | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615816/ https://www.ncbi.nlm.nih.gov/pubmed/34827615 http://dx.doi.org/10.3390/biom11111617 |
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