MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Zhenzhao Wang,Lili Liu,Zhen Li,Linna Li,Xingtong Liu,Rikun Cui,Fujun Yao,Lei Tian,Xiaofeng Kang,YanLi Guo
Intercalated binding of anthracycline anticancer drugs to DNA is associated with anticancer mechanisms. The i-motif, a cytosine-rich DNA secondary structure found in the promoter region of oncogenes, is a primary target for anticancer drugs action. Therefore, it is significant to study the interaction between anthracycline drugs and i-motif for cancer therapy using simple, rapid and low-cost analytical methods. Here, we utilized α-HL protein nanopore, which offers high sensitivity and high signal-to-noise ratio to investigate the conformational transition of human telomere i-motif induced by various anthracycline drugs at the single-molecule level. Our results revealed for the first time that anthracyclines drugs could induced the unfolding of i-motif into hairpin DNA. Additionally, our experiment captured the current signal of the intermediate state during the unfolding of i-motif into hairpin DNA, a signal difficult to obtain by conventional analytical tools such as circular dichroism (CD) and UV–visible spectroscopy (UV–vis). This research provides a novel tool for investigating the interaction between small molecule and DNA and lays the foundation for future screening of drugs acting on i-motif targets, as well as analyzing their therapeutic mechanism.
研究领域:
生物化学
·
分子生物学
·
药理学
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DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2020
·
IF 6.785
Lu Shi,Feifei Cao,Limin Zhang,Yang Tian
The development of switches responding to specific pH changes was particularly useful in wide application fields. Owing to flexible switches simulated by pH, i-motif DNAs are widely used as a pH sensor. But its character of structure transition strongly dependent on acidic pH severely hampers the application of i-motif DNA in physiological media. Herein, we report the stable i-motif structure formed at a physiological pH triggered by spatial confinement of silica nanochannels. Three classic DNA chains containing 21-mer i-motif domain base-pairs and a single-stranded multiply (T)n spacer, 5′-COOH-(T)n-CCCTAACCCTAACCCTAACCC-3′, were employed to evaluate the enhanced stability of i-motif structure. Compared to their free states in a dilute solution, the transition pH of all i-motif DNAs decorated in nanochannels remarkably shifts toward a neutral pH. Moreover, the transition midpoint can be tuned sensitively over the physiologically relevant pH range through slightly varying the length of T base spacer. Density functional theory (DFT) calculations validate that the increased proton density in a nanochannel triggers the formation of an i-motif structure under a neutral pH. Finally, this i-motif DNA based nanochannels electrode was successfully employed to monitor pH in brain microdialysates followed by cerebral ischemia. The present approach is not limited by fundamental investigation for DNA conformation but may extend toward the manipulation of i-motif based structures for artificial molecular machines and signaling systems.
研究领域:
生物化学
·
分子生物学
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医学检测
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DOI
PubMed
高影响因子
Journal of the American Chemical Society
·
2009
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IF 8.091
Yinghua Peng,Xiaohui Wang,Yi Xiao,Lingyan Feng,Chao Zhao,Jinsong Ren,Xiaogang Qu
The increasing worldwide demand for carbon nanotubes (CNTs) and increasing concern regarding how to safely develop and use CNTs are requiring a low-cost, simple, and highly sensitive CNT detection assay for toxicological evaluation and environmental monitoring. However, this goal is still far from being achieved. All the current CNT detection techniques are not applicable for automation and field analysis because they are dependent on highly expensive special instruments and complicated sample preparation. On the basis of the capability of single-walled carbon nanotubes (SWNTs) to specifically induce human telomeric i-motif formation, we design an electrochemical DNA (E-DNA) sensor that can distinguish single- and multiwalled carbon nanotubes both in buffer and in cell extracts. The E-DNA sensor can selectively detect SWNTs with a direct detection limit of 0.2 ppm and has been demonstrated in cancer cell extracts. To the best of our knowledge, this is the first demonstration of a biosensing technique that can distinguish different types of nanotubes. Our work will provide new insights into how to design a biosensor for detection of carbon nanotubes.
研究领域:
生物传感
·
环境监测
·
毒理学
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DOI
PubMed
高影响因子
ACS Sensors
·
2024
·
IF 8.2
Lin He,Yan Zhou,Min Zhang,Mingjian Chen,Yuchen Wu,Lanlin Qi,Lamei Liu,Bin Zhang,Xiaohai Yang,Xiaoxiao He,Kemin Wang
Detection of slight pH changes in skin interstitial fluid (ISF) is crucial yet challenging for studying pathological processes and understanding personal health conditions. In this work, we construct an i-motif DNA based fluorescent ratiometric microneedle sensing patch (IFR-pH MN patch) strategy that enables minimally invasive, high-resolution, and sensitive transdermal monitoring of small pH variations in ISF. The IFR-pH MN patch with advanced integration of both ISF sampling and pH sensing was fabricated from the cross-linking of gelatin methacryloyl and methacrylated hyaluronic acid, wrapping with pH-sensitive hairpin-containing i-motif DNA based fluorescent ratiometric probes in the matrix. Because it is mechanically robust for skin penetration and has high swelling ability, the IFR-pH MN patch could be quickly extracted as sufficient liquid from agarose gel (∼56.4 μL in 10 min). Benefiting from conformation changes of the hairpin-containing i-motif DNA under pH variation and ratiometric fluorescence signal readout, the IFR-pH MN patch could quantitate pH over a small range between pH 6.2 and 6.9 with an accuracy of 0.2 pH units in the mimic skin model. Furthermore, in vivo testing on wound and tumor mouse models indicated the ability of the biocompatible IFR-pH MN patch to penetrate the skin for obtaining transdermal pH values, demonstrating the potential applications in monitoring and intervention of pathological states.
研究领域:
生物医学工程
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分子生物学
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传感技术
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DOI
PubMed
高影响因子
Redox Biology
·
2025
·
IF 11.9
Dongsheng Ji,Jiahui Zhang,Jihai Liang,Zhi-Shu Huang,Bing Shu,Ding Li
Alzheimer's disease (AD) is a severe neurodegenerative disorder characterized by abnormal metabolism of β-amyloid (Aβ) precursor proteins and neuronal apoptosis, ultimately leading to cognitive dysfunction. The pathogenesis of AD is complex, and current single-target therapies are not effective in preventing the rapid progression of AD, which highlights the urgent need for developing multi-target drugs. In this study, a series of compounds were synthesized through a multi-targeting ligand strategy. After extensive screening and evaluation, we found a lead compound B14 , which showed excellent dual targeting ability for effectively alleviating neuronal apoptosis and oxidative stress damage of AD. In our molecular and cellular level experiments, B14 could target and stabilize the i-motif structure formed on the BCL-2 promoter to upregulate BCL-2 expression, which could also bind to Aβ and inhibit its deposition. In the Aβ 1-42 -induced cell model, B14 could maintain mitochondrial function and number, regulate intracellular reactive oxygen species (ROS) and Ca 2+ metabolism disorders, and effectively reduce Aβ 1-42 -induced apoptosis. Further studies showed that B14 also exhibited good ability to cross the blood-brain barrier (BBB), which significantly improved learning memory and cognitive deficits, reduced brain Aβ plaques, alleviated inflammation and restored oxidative stress markers in APP/PS1 mice. Our findings provide an innovative strategy of dual targeting BCL-2 promoter i-motif for transcriptional regulation and Aβ aggregation synergistically for mitigating AD pathologies. B14 represents a promising multi-target lead compound with a good potential for further development for AD treatment.
研究领域:
神经生物学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
NUCLEIC ACIDS RESEARCH
·
2025
·Vol. 53
·期 12
·
IF 13.1
Luo Tengshuo,Guan Ziyue,Liu Yunlong,Zhou Jun,Mergny Jean-Louis,Cheng Mingpan
A molecular beacon (MB) is an oligonucleotide probe with a stem-loop structure designed to fluoresce upon hybridization with a specific target nucleic acid. Herein, we introduce a novel i-motif DNA-based molecular beacon (iMB) designed for nucleic acid detection. DNA chemical sequencing showed that the iMB can be selectively opened when its target is present, thanks to the formation of a duplex between this target and the iMB recognition loop. Phase diagrams were introduced to analyze the binding properties between the iMB and its target, and to optimize the detection conditions with different combinations of pH and temperature. Benefiting from the environment-sensitive stability and special structural feature inherent to the i-motif, this iMB exhibits a controllable sensitivity and specificity through choosing appropriate temperature/pH combination and recognition loop position in the i-motif probe. Leveraging the duplex-specific nuclease (DSN) resistance of the i-motif, we significantly enhanced the sensitivity by more than four orders of magnitude through the implementation of a DSN-assisted amplification strategy. Finally, miRNAs in cell lines and patient plasma were detected by the iMBs, as validated via quantitative reverse transcription polymerase chain reaction (RT-qPCR). This research successfully broadens the structural repertoire of MB stems to include a pH- and temperature-responsive i-motif stem.
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DOI
PubMed
高影响因子
ORGANIC & BIOMOLECULAR CHEMISTRY
·
2018
·Vol. 16
·期 48
·9402-9408
·
IF 3.423
Pan Li,Zhe Chen,Yishun Huang,Jing Li,Fan Xiao,Shiyao Zhai,Zhiming Wang,Xuanjun Zhang,Leilei Tian
A new DNA-based fluorescent probe, which is a hybrid molecule of an i-motif forming sequence (IFS) and mono-functionalized tetraphenylethene (TPE), has been synthesized and investigated. A distinct pH-responsive aggregation-induced emission (AIE) effect has been observed from this hybrid molecule, i.e. the fluorescence of TPE will be turned on when the IFS part folds up under acidic conditions. According to the fact that a hybrid molecule with a relatively rigid structure shows a more obvious AIE effect, and whose nano-sized aggregates are formed at a high concentration, we assume that the solubility of the hybrid molecule in water will be reduced due to IFS folding, resulting in aggregation and the resultant AIE effect. Finally, due to its excellent pH responsiveness, this DNA-based probe employing an AIEgen has been applied in monitoring intracellular pH.
研究领域:
生物化学
·
分子生物学
·
分析化学
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DOI
PubMed
高影响因子
ACS Sensors
·
2020
·
IF 7.333
Dandan Zhao,Haoran Tang,Hao Wang,Cheng Yang,Yongxin Li
The nanopore-based technique is a useful tool for single-molecule sensing and characterization. In this work, we have developed a new DNA-functionalized gold-modified nanopore, and analytes can induce the conformational switch of i-motif DNA formed on the inner surface of the nanopore. i-Motif DNA structure can be formed in the presence of silver ions (Ag+), which will result in the change in surface charge and structure of the nanopore tip and ion current rectification (ICR) ratio. The i-motif DNA structure on nanopore surface will be destroyed after the addition of glutathione (GSH) due to the strong interaction of Ag–S bond, which results in the recovery of surface charge, steric hindrance, and ICR ratio. This analyte-triggered conformational switch of i-motif DNA can help us deeply understand the DNA technology inside single nanopore and will benefit the possible applications in an ultrasensitive detection and biological/chemical analysis.
研究领域:
纳米技术
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生物物理学
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分子生物学
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分析化学
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产品关联
DOI
PubMed
高影响因子
Journal of Analysis and Testing
·
2022
·Vol. 6
·期 1
·12-19
·
IF 0
Wang Xin-Yan,Li Yuanfang,Lv Shuzhen,Bi Sai
Herein, a dual-signal electrochemical biosensor has been developed by self-assembly of pH-activatable i-motif probes on magnetic microparticles (MMPs) coupled with DNA walker for signal amplification. In this study, the cytosine (C)-rich single-stranded DNAs are hybridized with DNA initiators to obtain the long-nicked duplexes with repeated units, which are further captured on MMPs to form the magnetic i-motif containers. The resulting duplexes contain abundant G–C base pairs, thus providing extensive binding sites for doxorubicin (DOX). At acidic pH, the C-rich sequences are folded into i-motif structure, resulting in the release of DOX and walker initiators. In this case, the liberated DOX is adsorbed on graphene quantum dots-modified glassy carbon electrode via π–π interaction, while the walker initiators as a moving part can catalyze the hybridization between MB-modified fueler DNA and tracker DNA on electrode, contributing to the generation of dual electrochemical signals induced by MB and DOX. Importantly, the magnetic separation can effectively reduce the background, achieving sensitive biosensing of pH ranging from 4.0 to 7.4 with excellent stability. Moreover, the proposed dual-signal electrochemical biosensor has been successfully applied for accurate monitoring of pH in human serum, which holds great potential in pH-dependent bioassays, especially in ultra-micro analysis for clinical applications.
研究领域:
生物化学
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分析化学
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医学诊断
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DOI
ANALYTICAL CHEMISTRY
·
2026
·Vol. 98
·期 37
·27381-27390
·
IF 7.3
Ju Huan,Ni Xiangna,Tan Yanqi,Song Zhiping,Chen Xiaoping,Ni Jiancong,Lin Zhenyu,Yang Weiqiang
Urease serves as a key diagnostic biomarker, whose abnormal
activity
is closely associated with oral diseases such as caries and periodontitis.
However, detecting trace urease in saliva remains technically challenging.
In this work, we report for the first time a C 4 -rGO-FET
biosensor by integrating a conformation-switchable C 4 -DNA
probe with an electrochemically reduced graphene oxide field-effect
transistor. The sensing mechanism relies on the pH-induced conformational
transition of C 4 -DNA between a folded i-motif and an unfolded
state, which effectively modulates the interfacial charge and thus
the carrier distribution in the rGO channel, resulting in a measurable
shift in the Dirac point voltage ( V CNP ). The designed sensor exhibits significantly enhanced pH response
(51.57 mV/pH) and reduces the Debye shielding effect. Upon urease-catalyzed
hydrolysis of urea, the resulting local pH increase triggers a positive V CNP shift, enabling highly sensitive detection
of urease activity. The biosensor demonstrates a wide linear range
(1–500 U/L), a low detection limit (0.18 U/L), and good reproducibility.
Moreover, it performs reliably in spiked human saliva samples, highlighting
its strong potential for point-of-care testing and real-time monitoring
in clinical diagnostics.
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高影响因子
ANALYTICA CHIMICA ACTA
·
2015
·
IF 4.513
Zhong Feng Gao,Dong Mei Chen,Jing Lei Lei,Hong Qun Luo,Nian Bing Li
Improving the reproducibility of electrochemical signal remains a great challenge over the past decades. In this work, i-motif oligonucleotide probe-based electrochemical DNA (E-DNA) sensor is introduced for the first time as a regenerated sensing platform, which enhances the reproducibility of electrochemical signal, for label-free detection of glucose and urea. The addition of glucose or urea is able to activate glucose oxidase-catalyzed or urease-catalyzed reaction, inducing or destroying the formation of i-motif oligonucleotide probe. The conformational switch of oligonucleotide probe can be recorded by electrochemical impedance spectroscopy. Thus, the difference of electron transfer resistance is utilized for the quantitative determination of glucose and urea. We further demonstrate that the E-DNA sensor exhibits high selectivity , excellent stability, and remarkable regenerated ability. The human serum analysis indicates that this simple and regenerated strategy holds promising potential in future biosensing applications.
研究领域:
分析化学
·
生物传感器
·
电化学
·
分子生物学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Huihui Yang,Jun Chen,Yuling Liang,Yanfei Zhang,Wen Yin,Yuzhi Xu,Si-Yang Liu,Zong Dai,Xiaoyong Zou
Dynamic imaging of cell surface pH is extremely challenging due to the slight changes in pH and the fast diffusion of secreted acid to the extracellular environment. In this work, we construct a novel metal–organic framework (MOF)-shell-confined i-motif-based pH probe (MOFC-i) strategy that enables sensitive and dynamic imaging of cell surface pH. The CY3- and CY5-labeled i-motif, which is hybridized via its short complementary chain with two-base mismatches, is optimized for sensing at physiological pH. After efficiently anchoring the optimized pH probes onto the cell membrane with the aid of cholesterol groups, a biocompatible microporous MOF shell is then formed around the cell by cross-linking ZIF-8 nanoparticles via tannic acid. The microporous MOF shell can confine secreted acid without inhibiting the normal physiological activities of cells; thus, the MOFC-i strategy can be used to monitor dynamic changes in the cell surface pH of living cells. Furthermore, this method can not only clearly distinguish the different metabolic behaviors of cancer cells and normal cells but also reveal drug effects on the cell surface pH or metabolism, providing promising prospects in pH-related diagnostics and drug screening.
研究领域:
生物化学
·
细胞生物学
·
分子生物学
·
生物医学工程
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DOI
PubMed
高影响因子
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