Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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
_version_ 1784604197092589568
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
work_keys_str_mv AT safitrifikaayu enhancementoftheimmunostimulatoryeffectofphosphodiestercpgoligodeoxynucleotidesbyanantiparallelguaninequadruplexstructuralscaffold
AT tuanhthitram enhancementoftheimmunostimulatoryeffectofphosphodiestercpgoligodeoxynucleotidesbyanantiparallelguaninequadruplexstructuralscaffold
AT hoshikazuaki enhancementoftheimmunostimulatoryeffectofphosphodiestercpgoligodeoxynucleotidesbyanantiparallelguaninequadruplexstructuralscaffold
AT shobomiwako enhancementoftheimmunostimulatoryeffectofphosphodiestercpgoligodeoxynucleotidesbyanantiparallelguaninequadruplexstructuralscaffold
AT zhaodandan enhancementoftheimmunostimulatoryeffectofphosphodiestercpgoligodeoxynucleotidesbyanantiparallelguaninequadruplexstructuralscaffold
AT witartoariefbudi enhancementoftheimmunostimulatoryeffectofphosphodiestercpgoligodeoxynucleotidesbyanantiparallelguaninequadruplexstructuralscaffold
AT sumarsonosonyheru enhancementoftheimmunostimulatoryeffectofphosphodiestercpgoligodeoxynucleotidesbyanantiparallelguaninequadruplexstructuralscaffold
AT girirachmanernawatiarifin enhancementoftheimmunostimulatoryeffectofphosphodiestercpgoligodeoxynucleotidesbyanantiparallelguaninequadruplexstructuralscaffold
AT tsukakoshikaori enhancementoftheimmunostimulatoryeffectofphosphodiestercpgoligodeoxynucleotidesbyanantiparallelguaninequadruplexstructuralscaffold
AT ikebukurokazunori enhancementoftheimmunostimulatoryeffectofphosphodiestercpgoligodeoxynucleotidesbyanantiparallelguaninequadruplexstructuralscaffold
AT yamazakitomohiko enhancementoftheimmunostimulatoryeffectofphosphodiestercpgoligodeoxynucleotidesbyanantiparallelguaninequadruplexstructuralscaffold