为核酸研究应用合理设计具有大斯托克斯位移的 G-四链选择性 "开启 "近红外荧光探针。

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2024-10-28 DOI:10.1021/acsabm.4c00940
Sajiya Parveen, Nirupa Chaurasia, Suchitra Gupta, Seema Vidyarthi, Nisha Gupta, Priyanka Pandey, Bhaskar Pant, Kinshuk Raj Srivastava, Niti Kumar, Atul Goel
{"title":"为核酸研究应用合理设计具有大斯托克斯位移的 G-四链选择性 \"开启 \"近红外荧光探针。","authors":"Sajiya Parveen, Nirupa Chaurasia, Suchitra Gupta, Seema Vidyarthi, Nisha Gupta, Priyanka Pandey, Bhaskar Pant, Kinshuk Raj Srivastava, Niti Kumar, Atul Goel","doi":"10.1021/acsabm.4c00940","DOIUrl":null,"url":null,"abstract":"<p><p>Guanine-rich DNA/RNA sequences can form Hoogsteen bonds to adopt noncanonical secondary structures called G-quadruplexes, and these have been associated with diverse cellular processes. There has been considerable research interest in the design of G4-interacting ligands for cellular probing of the G4 structure and understanding its associated biological function. Most of the fluorescent G4 ligands either do not have significant selectivity over other nucleic acid structures, have high Stokes shift, or are not in the near-infrared (NIR) region, which limits its cellular visualization. The current work involves the rational design and synthesis of NIR fluorescent probes comprising a (Z)-1-methyl-2-((3-methylbenzo[d]thiazol-2(3H)-ylidene)methyl)quinolin-1-ium scaffold. Among the designed molecules, <b>4a</b> exhibited far-red fluorescence (λ<sub>max</sub> = 680 nm) with large Stokes shift (∼182 nm) upon selective binding to human telomeric G-quadruplexes. The dye <b>4a</b> does not disturb the conformation and stability of G-quadruplexes, thereby making it suitable for nucleic acid research based applications. Interestingly, <b>4a</b> showed remarkable selectivity over single- and double-stranded structures in contrast to a commercially available quadruplex binding probe, Thiazole orange (TO). The molecular docking studies indicate that <b>4a</b> binds at the groove region of the telomeric DNA G-quadruplex through π-π stacking interactions with the quinoline and amine-substituted phenyl ring and with the phosphate backbone through anion-π interactions with the benzothiazole ring. The designed molecule <b>4a</b> has interesting photophysical properties, cell permeability, and biocompatibility with minimal cytotoxicity. Fluorescence imaging studies in live HeLa cells showed that probe <b>4a</b> binds to the transient population of the DNA G-quadruplex in the nucleus and RNA quadruplexes in the cytoplasm. In brief, G-quadruplex NIR fluorescent probe <b>4a</b> with a higher signal/noise ratio has significant potential for cellular imaging studies and thus opens avenues to decipher the biological pathways for better understanding of G-quadruplex biology.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Rationally Designed G-Quadruplex Selective \\\"Turn-On\\\" NIR Fluorescent Probe with Large Stokes Shift for Nucleic Acid Research-Based Applications.\",\"authors\":\"Sajiya Parveen, Nirupa Chaurasia, Suchitra Gupta, Seema Vidyarthi, Nisha Gupta, Priyanka Pandey, Bhaskar Pant, Kinshuk Raj Srivastava, Niti Kumar, Atul Goel\",\"doi\":\"10.1021/acsabm.4c00940\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Guanine-rich DNA/RNA sequences can form Hoogsteen bonds to adopt noncanonical secondary structures called G-quadruplexes, and these have been associated with diverse cellular processes. There has been considerable research interest in the design of G4-interacting ligands for cellular probing of the G4 structure and understanding its associated biological function. Most of the fluorescent G4 ligands either do not have significant selectivity over other nucleic acid structures, have high Stokes shift, or are not in the near-infrared (NIR) region, which limits its cellular visualization. The current work involves the rational design and synthesis of NIR fluorescent probes comprising a (Z)-1-methyl-2-((3-methylbenzo[d]thiazol-2(3H)-ylidene)methyl)quinolin-1-ium scaffold. Among the designed molecules, <b>4a</b> exhibited far-red fluorescence (λ<sub>max</sub> = 680 nm) with large Stokes shift (∼182 nm) upon selective binding to human telomeric G-quadruplexes. The dye <b>4a</b> does not disturb the conformation and stability of G-quadruplexes, thereby making it suitable for nucleic acid research based applications. Interestingly, <b>4a</b> showed remarkable selectivity over single- and double-stranded structures in contrast to a commercially available quadruplex binding probe, Thiazole orange (TO). The molecular docking studies indicate that <b>4a</b> binds at the groove region of the telomeric DNA G-quadruplex through π-π stacking interactions with the quinoline and amine-substituted phenyl ring and with the phosphate backbone through anion-π interactions with the benzothiazole ring. The designed molecule <b>4a</b> has interesting photophysical properties, cell permeability, and biocompatibility with minimal cytotoxicity. Fluorescence imaging studies in live HeLa cells showed that probe <b>4a</b> binds to the transient population of the DNA G-quadruplex in the nucleus and RNA quadruplexes in the cytoplasm. In brief, G-quadruplex NIR fluorescent probe <b>4a</b> with a higher signal/noise ratio has significant potential for cellular imaging studies and thus opens avenues to decipher the biological pathways for better understanding of G-quadruplex biology.</p>\",\"PeriodicalId\":2,\"journal\":{\"name\":\"ACS Applied Bio Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-10-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Bio Materials\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1021/acsabm.4c00940\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MATERIALS SCIENCE, BIOMATERIALS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1021/acsabm.4c00940","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 0

摘要

富含鸟嘌呤的 DNA/RNA 序列可以形成胡格斯泰因键(Hoogsteen bonds),从而形成被称为 G 型四联体的非正则二级结构,这些结构与多种细胞过程有关。人们对设计与 G4 相互作用的配体以在细胞内探测 G4 结构并了解其相关生物功能的研究兴趣浓厚。大多数 G4 荧光配体要么对其他核酸结构没有明显的选择性,要么具有较高的斯托克斯偏移,要么不在近红外(NIR)区域,从而限制了其在细胞中的可视化。目前的工作涉及合理设计和合成由 (Z)-1- 甲基-2-((3-甲基苯并[d]噻唑-2(3H)-亚基)甲基)喹啉-1-鎓支架组成的近红外荧光探针。在所设计的分子中,4a 在选择性地与人类端粒 G-四联体结合后,显示出远红荧光(λmax = 680 nm)和较大的斯托克斯偏移(∼182 nm)。染料 4a 不会干扰 G-四联体的构象和稳定性,因此适用于基于核酸的研究应用。有趣的是,与市场上销售的四重结合探针噻唑橙(TO)相比,4a 对单链和双链结构具有显著的选择性。分子对接研究表明,4a 通过与喹啉和胺取代的苯基环的π-π堆积相互作用,以及通过与苯并噻唑环的阴离子-π相互作用,与磷酸骨架结合在端粒 DNA G-四链的沟区域。所设计的分子 4a 具有有趣的光物理特性、细胞渗透性和生物相容性,细胞毒性极低。在活体 HeLa 细胞中进行的荧光成像研究表明,探针 4a 能与细胞核中的 DNA G-四联体和细胞质中的 RNA 四联体瞬时群结合。简而言之,G-四联体近红外荧光探针 4a 具有更高的信噪比,在细胞成像研究中具有巨大潜力,从而为破译生物通路、更好地理解 G-四联体生物学开辟了途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Rationally Designed G-Quadruplex Selective "Turn-On" NIR Fluorescent Probe with Large Stokes Shift for Nucleic Acid Research-Based Applications.

Guanine-rich DNA/RNA sequences can form Hoogsteen bonds to adopt noncanonical secondary structures called G-quadruplexes, and these have been associated with diverse cellular processes. There has been considerable research interest in the design of G4-interacting ligands for cellular probing of the G4 structure and understanding its associated biological function. Most of the fluorescent G4 ligands either do not have significant selectivity over other nucleic acid structures, have high Stokes shift, or are not in the near-infrared (NIR) region, which limits its cellular visualization. The current work involves the rational design and synthesis of NIR fluorescent probes comprising a (Z)-1-methyl-2-((3-methylbenzo[d]thiazol-2(3H)-ylidene)methyl)quinolin-1-ium scaffold. Among the designed molecules, 4a exhibited far-red fluorescence (λmax = 680 nm) with large Stokes shift (∼182 nm) upon selective binding to human telomeric G-quadruplexes. The dye 4a does not disturb the conformation and stability of G-quadruplexes, thereby making it suitable for nucleic acid research based applications. Interestingly, 4a showed remarkable selectivity over single- and double-stranded structures in contrast to a commercially available quadruplex binding probe, Thiazole orange (TO). The molecular docking studies indicate that 4a binds at the groove region of the telomeric DNA G-quadruplex through π-π stacking interactions with the quinoline and amine-substituted phenyl ring and with the phosphate backbone through anion-π interactions with the benzothiazole ring. The designed molecule 4a has interesting photophysical properties, cell permeability, and biocompatibility with minimal cytotoxicity. Fluorescence imaging studies in live HeLa cells showed that probe 4a binds to the transient population of the DNA G-quadruplex in the nucleus and RNA quadruplexes in the cytoplasm. In brief, G-quadruplex NIR fluorescent probe 4a with a higher signal/noise ratio has significant potential for cellular imaging studies and thus opens avenues to decipher the biological pathways for better understanding of G-quadruplex biology.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
期刊最新文献
Glycocalyx Interactions Modulate the Cellular Uptake of Albumin-Coated Nanoparticles. Emerging Technological Advancement for Chronic Wound Treatment and Their Role in Accelerating Wound Healing. Biosynthesis of pH-Responsive Mesoporous Silica Nanoparticles from Cucumber Peels for Targeting 3D Lung Tumor Spheroids. Nanobioengineered Al2O3 Core-Shell Nanoparticle Preparation Using Bauhinia Variegate Plant Extract for Efficient Photocatalysis and Electrochemical Sensing. Rationally Designed G-Quadruplex Selective "Turn-On" NIR Fluorescent Probe with Large Stokes Shift for Nucleic Acid Research-Based Applications.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1