INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Min Zou,Jing-Yan Li,Meng-Jia Zhang,Jun-Hui Li,Jun-Tao Huang,Pei-Dan You,Shu-Wen Liu,Chun-Qiong Zhou
At present, there are still no anti-Zika virus (ZIKV) drugs or vaccines approved by FDA with accurate targets and antiviral mechanisms. Considering the RNA G-quadruplex sequences in ZIKV genome, it is very meaningful to develop G-quadruplex binders as potential anti-ZIKV drugs with novel and accurate targets. In this paper, five classical G-quadruplex binders including Ber , Braco 19 , NiL , 360A and PDS have been chosen to discuss their interaction with ZIKV RNA G-quadruplexes. PDS shows higher binding affinity and thermal stability than the other G-quadruplex binders. This property is further evidenced in cells by immunofluorescence microscopy. And PDS shows higher anti-ZIKV activity (EC 50 = 4.2 ± 0.4 μM) than the other G-quadruplex binders as well as the positive control ribavirin, with a low cytotoxicity. By time-of-addition assay, PDS exerts antiviral activity at the post-entry process of ZIKV replication cycle, thus inhibiting ZIKV mRNA replication and protein expression. Furthermore, PDS combines with ZIKV NS2B-NS3 protease and reduces its catalytic activity. This study suggests that G-quadruplex binder PDS is an effective multi-target ZIKV inhibitor, which provides more guidance to design some novel anti-ZIKV drugs targeting ZIKV RNA G-quadruplexes.
研究领域:
病毒学
·
药物化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2012
·
IF 4.555
Ruimin Li,Cen Xiong,Zhiyou Xiao,Liansheng Ling
A novel colorimetric method for detection of cholesterol was developed with hemin-G-quadruplex DNAzyme by transducing oxidation of cholesterol into the color change of 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS 2− ). Oligonucleotide 5′-GTGGGTAGGGCGGGTTGG-3′ (Oligo-1) formed G-quadruplex structure in the presence of K + , it acted as a horseradish peroxidase (HRP) mimicking DNAzyme when binding hemin and catalyzed the oxidation of colorless ABTS 2− to green ABTS − by H 2 O 2 , which was produced by the reaction of cholesterol and oxygen that catalyzed by cholesterol oxidase. Therefore, the oxidation of cholesterol could be transduced into the color change of ABTS 2− by combining these two reactions. Under the optimum conditions, the absorbance was proportional to the concentration of cholesterol over the range of 1.0–30 μM, with a linear regression equation of A = 0.362 + 0.0256 C ( C : μM, R = 0.998) and a detection limit of 0.10 μM (3 σ /slope). Moreover, the practicability of the assay in the detection of cholesterol in human serum was studied as well.
研究领域:
生物化学
·
医学诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2014
·
IF 3.511
Xiaohua Jiang,Huimin Zhang,Jun Wu,Xiang Yang,Jingwei Shao,Yujing Lu,Bin Qiu,Zhenyu Lin,Guonan Chen
In this paper, a novel label-free G-quadruplex DNAzyme sensor has been proposed for colorimetric identification of GMO using CaMV 35S promoter sequence as the target. The binary probes can fold into G-quadruplex structure in the presence of DNA-T (Target DNA) and then combine with hemin to form a DNAzyme resembling horseradish peroxidase . The detection system consists of two G-rich probes with 2:2 split mode by using the absorbance and color of ABTS 2− as signal reporter. Upon the addition of a target sequence, two probes both hybridize with target and then their G-rich sequences combine to form a G-quadruplex DNAzyme, and the DNAzyme can catalyze the reaction of ABTS 2− with H 2 O 2 . Then the linear range is from 0.05 to 0.5 μM while detection limit is 5 nM. These results demonstrate that the proposed G-quadruplex DNAzyme method could be used as a simple, sensitive and cost-effective approach for assays of GMO.
研究领域:
生物化学
·
分子生物学
·
食品科学
✓ 已验证
DOI
高影响因子
ANALYTICA CHIMICA ACTA
·
2012
·
IF 4.555
Sai Bi,Yangyang Cui,Li Li
Considering the great significance of microRNAs (miRNAs) in cancer detection and typing, the development of sensitive, specific, quantitative, and low-cost methods for the assay of expression levels of miRNAs is desirable. We describe a highly efficient amplification platform for ultrasensitive analysis of miRNA (taking let-7a miRNA as a model analyte) based on a dumbbell probe-mediated cascade isothermal amplification (DP-CIA) strategy. The method relies on the circularization of dumbbell probe by binding target miRNA, followed by rolling circle amplification (RCA) reaction and an autonomous DNA machine performed by nicking/polymerization/displacement cycles that continuously produces single-stranded G-quadruplex to assemble with hemin to generate a color signal. In terms of the high sensitivity (as low as 1 zmol), wide dynamic range (covering 9 orders of magnitude), good specificity (even single-base difference) and easy operation (one probe and three enzymes), the proposed label-free assay is successfully applied to direct detection of let-7a miRNA in real sample (total RNA extracted from human lung tissue), demonstrating an attractive alternative for miRNA analysis for gene expression profiling and molecular diagnostics, particularly for early cancer diagnosis.
研究领域:
分子生物学
·
医学诊断
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2021
·
IF 7.46
Jiao Zhou,Min Qing,Yu Ling,Lei Wang,Nian Bing Li,Hong Qun Luo
DNAzyme and G-quadruplex are purposed as universal recognition elements to achieve multi-functional signal amplification and readout, showing great potential in the design of biosensors and nanodevices. Herein, the single-stranded DNA (ssDNA) opens the dumbbell-shaped hairpin probes, the generated double-stranded DNA (dsDNA) is constructed as a nanobridge, and the released G-rich sequence is folded into a G-quadruplex village. The fluorescence of crystal violet/G-quadruplex complex villages is enhanced by the dsDNA nanobridge connections. Under the excitation wavelength of 580 nm, the fluorescence emission intensity at 624 nm exhibits a good linearity with the concentration of crystal violet (CV) in the range of 10–250 nM, which can be used for sensitive detection of CV . Additionally, combined with Pb 2+ -dependent DNAzyme, a platform for quantitative detection of Pb 2+ is established. In the concentration range of 5 nM – 25 μM, the fluorescence signal increases with the increase of Pb 2+ concentration. The quantitative detection limit of Pb 2+ by this method is 5 nM, and it possesses good selectivity and recovery for Pb 2+ in a variety of water samples. More importantly, the platform can sensitively detect various metal ions by changing the DNAzyme sequence. It has potential application in the field of environmental monitoring.
研究领域:
生物化学
·
纳米技术
·
分析化学
·
环境科学
✓ 已验证
产品关联
DOI
高影响因子
ANALYTICAL LETTERS
·
2021
·
IF 2.329
Minting Wang,Liting Zhao,Yanmei Wen,Yulian Wu,Yubin Li
Simian virus 40 (SV40) causes multiple diseases due to its low immunogenicity and strong infectivity. Here, the development of a label-free fluorescent sensor designed to detect double-stranded DNA (dsDNA) via a functionalized molecular beacon (MB) produced using triplex DNA and guanine (G)-quadruplexes is described. A SV40-specific dsDNA sequence was used as the target dsDNA (T-dsDNA). The MB was designed to comprise a G-quadruplex sequence, a complementary homopyrimidine sequence for T-dsDNA, and a partially complementary sequence for G-quadruplex sequence. Addition of T-dsDNA forces the MB to unfold, forming triplex DNA, and releasing the G-quadruplex sequence that binds to N-methyl mesoporphyrin IX (NMM), producing a signal. The G-quadruplex/NMM complex augments the signal at 610 nm and allows qualitative SV40 detection. Under optimal conditions, this strategy demonstrates a low limit of detection (0.4 nM). Compared to traditional biosensors, this sensor is enzyme-free, rapid, selective, sensitive, and was used to determine T-dsDNA in serum, suggesting that this strategy has applications in clinical analysis and for other viruses.
研究领域:
生物化学
·
病毒学
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
SENSORS
·
2013
·Vol. 13
·期 1
·1064-1075
·
IF 1.953
Zhenzhu Zheng,Jing Han,Wensheng Pang,Juan Hu
With an internal transcribed spacer of 18 S, 5.8 S and 26 S nuclear ribosomal DNA (nrDNA ITS) as DNA marker, we report a colorimetric approach for authentication ofPseudostellaria heterophylla(PH) and its counterfeit species based on the differentiation of the nrDNA ITS sequence. The assay possesses an unlabelled G-quadruplex DNAzyme molecular beacon (MB) probe, employing complementary sequence as biorecognition element and 1:1:1:1 split G-quadruplex halves as reporter. In the absence of target DNA (T-DNA), the probe can shape intermolecular G-quadruplex structures capable of binding hemin to form G-quadruplex-hemin DNAzyme and catalyze the oxidation of ABTS2−to blue-green ABTS•−by H2O2. In the presence of T-DNA, T-DNA can hybridize with the complementary sequence to form a duplex structure, hindering the formation of the G-quadruplex structure and resulting in the loss of the catalytic activity. Consequently, a UV-Vis absorption signal decrease is observed in the ABTS2−-H2O2system. The “turn-off” assay allows the detection of T-DNA from 1.0 × 10−9to 3.0 × 10−7mol·L−1(R2= 0.9906), with a low detection limit of 3.1 × 10−10mol·L−1. The present study provides a sensitive and selective method and may serve as a foundation of utilizing the DNAzyme MB sensor for identifying traditional Chinese medicines.Keywords:G-quadruplex DNAzyme;molecular beacon;colorimetric;Pseudostellaria heterophylla
研究领域:
生物化学
·
分子生物学
·
分析化学
·
中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 4
·1529
·
IF 4.6
Zhixiang Wang,Wentao Liu,Guohu Li,Jiacheng Wang,Bin Zhao,Peishan Huang,Wenjie Mei
Herein, two novel ruthenium(II) complexes coupled by erianinviaa flexible carbon chain, [Ru(phen)2(L1-(CH2)4-erianin)](ClO4)2(L1= 2-(2-(tri-fluoromethyphenyl))-imidazo [4,5f][1–10]phenanthroline (1) and [Ru(phen)2(L2-(CH2)4-eria)](ClO4)2(L2= 2-(4-(tri-fluoromethyphenyl))-imidazo [4,5f][1,10]phenanthroline (2), have been synthesized and investigated as a potential G-quadruplex(G4) DNA stabilizer. Both complexes, especially 2, can bind toc-mycG4 DNA with high affinity by electronic spectra, and the binding constant calculated for 1 and 2 is about 15.1 and 2.05 × 107M−1, respectively. This was further confirmed by the increase in fluorescence intensity for both complexes. Moreover, the positive band at 265 nm in the CD spectra ofc-mycG4 DNA decreased treated with 2, indicating that 2 may bind toc-mycG4 DNA through extern groove binding mode. Furthermore, fluorescence resonance energy transfer (FRET) assay indicated that the melting point ofc-mycG4 DNA treated with 1 and 2 increased 15.5 and 16.5 °C, respectively. Finally, molecular docking showed that 1 can bind toc-mycG4 DNA in the extern groove formed by base pairs G7–G9 and G22–A24, and 2 inserts into the small groove ofc-mycG4 DNA formed by base pairs T19–A24. In summary, these ruthenium(II) complexes, especially 2, can be developed as potentialc-mycG4 DNA stabilizers and will be exploited as potential anticancer agents in the future.Keywords:ruthenium(II) complexes;erianin;c-mycG-quadruplex DNA;stabilizer
研究领域:
生物化学
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Microbiology Spectrum
·
2022
·Vol. 10
·期 3
·
IF 9.043
Lu Lv,Leiliang Zhang
Human enteroviruses cause many diseases; however, there is no specific therapeutic drug. G-quadruplex is an atypical secondary structure formed in the guanine rich region of DNA or RNA, which can exist in the viral genome. The different positions of G-quadruplex play an important role in the regulation of virus replication and infection. Whether G-quadruplexes are present in human enteroviruses is unknown. In current study, we analyzed the potential quadruplex forming sequences of human enteroviruses, especially EV-A71 virus, which causes hand, foot, and mouth disease. The results showed that there were a certain number of potential quadruplex-forming sequences in human enteroviruses. Through a variety of experimental methods, we evaluated the formation potential of EV-A71 encoded G-quadruplex and analyzed the binding ability of G-quadruplex ligands, including BRACO-19, pyridostatin and TMPyP4 to virus encoded G-quadruplexes. G-quadruplex ligands BRACO-19, PDS and TMPyP4 could inhibit the transcription of constructs containing EV-A71 G-quadruplex sequences. Moreover, we found that BRACO-19 was able to inhibit the replication of EV-A71, suggesting that targeting G-quadruplexes in EV-A71 genome by G-quadruplex ligands could be a novel antiviral way against EV-A71. Our finding not only uncovered the G-quadruplexes in human enteroviruses, but also would provide a new strategy for human enteroviruses therapy.IMPORTANCE G-quadruplex is a stable nucleic acid secondary structure formed by the folding of guanine rich nucleic acid. The important regulatory function of G-quadruplex makes it an attractive target of antiviral effect. Human enteroviruses cause a variety of human diseases, including common cold, nervous system diseases, cardiovascular damage, and diabetes. Enterovirus A71 (EV-A71) is one of pathogens causing hand, foot, and mouth disease; however, whether G-quadruplexes are present in the genomes of human enteroviruses is unknown. The function of G-quadruplexes in the EV-A71 genomes is not clear. We predicted and characterized G-quadruplex sequences in EV-A71. G-quadruplex ligands were identified to stabilize EV-A71 G-quadruplexes with high affinities. We also demonstrated G-quadruplex ligand BRACO-19 inhibited EV-A71 replication. Our studies provide a framework for targeting G-quadruplexes in the enteroviruses genome, which will be a new way to develop antiviral agents against human enteroviruses.
研究领域:
分子生物学
·
病毒学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS
·
2014
·Vol. 14
·期 12
·22971-22981
·
IF 2.048
Zhenzhu Zheng,Juan Hu,Zhaodong He
A label-free split G-quadruplex and graphene oxide (GO)-based fluorescence platform has been designed to distinguishPseudostellaria heterophylla(PH) from its adulterants based on the differences in their nrDNA ITS sequences. Herein, GO has been first introduced to capture G-rich probes with 2:2 split mode and then decrease the background signal. As T-DNA exists, the probes leave the GO surface to form double-stranded structures followed by the formation of the overhanging G-rich sequence into a G-quadruplex structure, which combines quinaldine red specifically to produce a strong fluorescence signal. In addition, this strategy allows detection of T-DNA in a wide range of concentrations from 1.0 × 10−8to 2.0 × 10−6mol·L−1with a detection limit of 7.8 × 10−9mol·L−1. We hope that the split G-quadruplex/GO platform can be utilized to further develop gene identification sensors in Traditional Chinese Medicine or other analysis areas.Keywords:split G-quadruplex;graphene oxide;fluorescence;Pseudostellaria heterophylla
研究领域:
中药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2017
·
IF 3.887
Li-Hong Ma,Hai-Bo Wang,Bi-Yun Fang,Fang Tan,Yuan-Cheng Cao,Yuan-Di Zhao
In this paper, visual detection of trace lead ion was established by aptamer and silver staining. The basic strategy was that aminated PS2.M aptamer was immobilized onto slide and formed stable G-quadruplex structure. PbS was generated by adding S 2− , and it catalyzed subsequent silver staining reaction, through the silver staining amplification effect, the slide presented visible ash black. The gray value of slide after silver staining was analyzed and the semi-quantitative detection of Pb 2+ in solution was realized. The results showed that optical darkness ratio (ODR) and logarithmic value of Pb 2+ concentration had a good linear relationship (R 2 = 0.951) over the range of 0.5–10 μM. In addition, there was no obvious interference of other common metal ions for the detection, indicating that this method presented outstanding selectivity. And it was also used for qualitative and semi-quantitative determination of Pb 2+ in soil sample successfully.
研究领域:
生物化学
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2016
·Vol. 183
·期 11
·2965-2971
·
IF 4.831
Meng Yan,Hun Xu,Zhang Yue,Luo Xiliang
A toehold-aided DNA recycling amplification technology was developed based on the combination of toehold-aided DNA recycling and the hemin/G-quadruplex label. The dsDNA formed between aptamer and DNA1 was first immobilized on magnetic beads. On addition of target analyte (exemplified here for riboflavin), the aptamer-riboflavin complex is formed and DNA1 is released by the beads. After magnetic separation, the supernatant containing the released DNA1 is added to a solution containing the hairpin capture DNA on magnetic beads. DNA1 will hybridize with the hairpin capture DNA via toehold binding and branch migration. This process will open the hairpin structure, and an external toehold is formed in the newly formed dsDNA. On addition of reporter DNA containing the G-quadruplex, it will interact with the formed dsDNA via toehold binding and branch migration, resulting in the releasing of DNA1 and capturing of reporter DNA on the magnetic beads. The released DNA1 will bind to another hairpin capture DNA which can start another round of DNA1 recycling. Chemiluminescence (CL) is generated by the G-quadruplex-hemin-luminol CL reaction system. Under optimal conditions, the calibration plot is linear in the 0.1 to 700 nM riboflavin concentration range, with a 30 pM detection limit (at a signal-to-noise ratio of 3). The method was successfully applied to the quantitation of riboflavin in spiked urine samples.
Toehold-aided DNA recycling coupled with hemin G-quadruplex for target detection.
研究领域:
生物化学
·
分析化学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）