Effects of G-Quadruplex Ligands on the Topology, Stability, and Immunostimulatory Properties of G-Quadruplex-Based CpG Oligodeoxynucleotides

CpG寡核苷酸 TLR9型 核酸酶 CpG站点 化学 G-四倍体 核酸 免疫系统 鸟嘌呤 拓扑(电路) 生物 DNA DNA甲基化 基因 生物化学 核苷酸 基因表达 免疫学 组合数学 数学
作者
Anh Thi Tram Tu,Kazuaki Hoshi,Yue Ma,Taiji Oyama,Satoko Suzuki,Kaori Tsukakoshi,Kazuo Nagasawa,Kazunori Ikebukuro,Tomohiko Yamazaki
出处
期刊:ACS Chemical Biology [American Chemical Society]
卷期号:17 (7): 1703-1713 被引量:4
标识
DOI:10.1021/acschembio.1c00904
摘要

We previously reported that the formation of guanine-quadruplex (G4) structures provides phosphodiester oligodeoxynucleotides containing unmethylated cytosine-phosphate-guanine (CpG ODNs) with higher nuclease resistance and cellular uptake, thereby increasing their immunostimulation efficiency through TLR9 activation. CpG ODNs forming G4 structures (G4 CpG ODNs) are thus potential vaccine adjuvants against infectious diseases. However, the G4 structure changes topology depending on the surrounding environment. Recently, G4 ligands, which are small molecules that bind to G4 ODNs with high affinity, were reported to improve the stability of G4. In this study, we propose to increase the stability and function of G4 CpG ODNs using G4 ligands. We show the effects of two G4 ligands, named L2H2-6OTD (L2H2) and L2G2-2M2EG-6OTD (L2G2), on the topology, stability, and immunostimulatory properties of a monomeric hybrid-type G4 CpG ODN containing CpG motifs in the central loop, named GD3. We found that L2H2 helps maintain the hybrid G4 topology of GD3, whereas L2G2 induces parallel G4 formation. Both G4 ligands increase the thermodynamic and nuclease stability of GD3. However, only GD3 associated with L2H2 binds efficiently to TLR9 and evokes a higher immune response from mouse macrophage-like RAW264 cells. GD3 associated with L2G2 does not bind efficiently to TLR9 and elicits lower cytokine production. Our results demonstrate that the potential to enhance immunostimulatory properties depends on the ability of G4 ligands to maintain and stabilize the hybrid G4 of GD3. We anticipate that our findings will facilitate the development of more effective G4 CpG ODN-based vaccine adjuvants against infectious diseases.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
2秒前
千跃应助ZY采纳,获得10
3秒前
5秒前
Grondwet发布了新的文献求助10
5秒前
6秒前
西小喵发布了新的文献求助10
6秒前
wwl发布了新的文献求助10
7秒前
Notdodead应助希望采纳,获得10
7秒前
科研通AI5应助xyj6486采纳,获得10
7秒前
8秒前
智慧者完成签到,获得积分10
8秒前
zebra8848发布了新的文献求助10
9秒前
9秒前
9秒前
孙燕应助淳于安筠采纳,获得30
10秒前
11秒前
幸福大白发布了新的文献求助30
11秒前
wsj发布了新的文献求助10
13秒前
ZONG发布了新的文献求助20
13秒前
wuy发布了新的文献求助10
15秒前
16秒前
17秒前
17秒前
Jun关闭了Jun文献求助
17秒前
星星发布了新的文献求助10
18秒前
20秒前
射天狼发布了新的文献求助10
20秒前
20秒前
20秒前
zebra8848完成签到,获得积分10
20秒前
21秒前
深情安青应助wsj采纳,获得10
21秒前
21秒前
sxy发布了新的文献求助10
22秒前
蔡从安发布了新的文献求助10
23秒前
24秒前
柔弱云朵完成签到,获得积分10
25秒前
25秒前
25秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3989444
求助须知:如何正确求助?哪些是违规求助? 3531531
关于积分的说明 11254250
捐赠科研通 3270191
什么是DOI,文献DOI怎么找? 1804901
邀请新用户注册赠送积分活动 882105
科研通“疑难数据库(出版商)”最低求助积分说明 809174