ANALYTICAL CHEMISTRY
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2015
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IF 5.636
Nannan Liu,Zekun Yang,Xiaoding Lou,Benmei Wei,Juntao Zhang,Pengcheng Gao,Ruizuo Hou,Fan Xia
Almost all of the important functions of DNA are realized by proteins which interact with specific DNA, which actually happens in a limited space. However, most of the studies about the protein–DNA binding are in an unconfined space. Here, we propose a new method, nanopore-based DNA-probe sequence-evolution (NDPSE), which includes up to 6 different DNA-probe systems successively designed in a nanoscale confined space which unveil the more realistic characteristics of protein–DNA binding phenomena. There are several features; for example, first, the edge-hindrance and core-hindrance contribute differently for the binding events, and second, there is an equilibrium between protein–DNA binding and DNA–DNA hybridization.
研究领域:
分子生物学
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生物信息学
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生物物理学
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DOI
PubMed
高影响因子
Chemistry-An Asian Journal
·
2025
·
IF 3.3
Lin Li,Wen Lu,Huayu Xue,Shilong Yang,Mengyi Zhou,Li Xu
A series of Dehydroabietylamine (DHAA) C-ring Schiff derivatives, L3-L20, were synthesized and their in vitro cytotoxic activity against the human tumor cell lines cervix HeLa, breast MCF-7, lung A549, liver HepG2, and the nonmalignant cell line umbilical vein HUVEC was investigated. Most of the compounds showed varying degrees of anticancer activity against HeLa cell lines while demonstrating lower toxicity to normal HUVEC cells compared to DHAA and doxorubicin (DOX), especially compound L19, which not only enhanced the anticancer activity of DHAA, but also significantly reduced the toxicity to normal cells, achieving a selectivity index (SI) 118 times higher than that of DHAA and 245 times higher than that of DOX. In addition, compound L19 induced apoptosis in HeLa cells in a dose-dependent manner and arrested the cell cycle in S phase. Spectroscopic experiments and molecular docking results showed that there was a strong interaction between the compounds and DNA. All these results indicate that the introduction of Schiff base structure on the C-ring of DHAA is an effective strategy for enhancing its selectivity, providing new insights for the design of DHAA-based anticancer compounds
研究领域:
药理学
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肿瘤学
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药物化学
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分子生物学
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DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2018
·
IF 5.667
Yanhua He,Xiaoye Wen,Bingyan Zhang,Zhefeng Fan
We coupled single-stranded DNA-binding protein (SSB) with graphene oxide quantum dots (GOQDs) to form QDs–SSB, as a new type of fluorescent probe. Considering the superiority of FRET and the urgency of realizing kanamycin (KAN) sensitive detection, we combined this fluorescent probe with Apt-BHQ 1 , and applied the FRET principle to achieve ultra-trace detection of KAN. The superiority of detection depends on: SSB has a strong affinity for aptamer (apt) in free state but not in collapsed state; The aptamer is in a free state when not bound to the target and is folded when combined with the target. In the absence of KAN, the fluorescence of the QDs–SSB was quenched by Apt-BHQ 1 via FRET. However, when the KAN was added to the QDs–SSB/apt-BHQ 1 system, the combination of aptamer with KAN caused the aptamer to assume a folded state and lose its ability to bind with SSB, thereby reducing FRET and the fluorescence of QDs–SSB recovery. The detection limit of this aptasensor was low to 6 pg/mL with a linear range of 0.01–90 ng/mL. Moreover, the method had high selectivity, stability, and anti-interference. Thus, this is a promising method that can be widely used for biological detection.
研究领域:
生物化学
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分析化学
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生物技术
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DOI
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
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2025
·
IF 4.7
Yunkai Sun,Qingqing Song,Meng Cao,Chunhong Tan,Xiao-Feng Wang,Kejie Du,Yuheng Zhang,Yi Ding,Xiaoqiang Xue
Metal-organic complexes, particularly copper complexes, are emerging as promising candidates for anticancer drug due to their versatile redox states. Two copper complexes ( complex1 and complex2 ) have been designed based on the ligands for 1,10-phenanthroline (phen), 4,5-diazofluoren-9-one (DAFO) and 1,4-terephthalic acid (1,4-BDC), and the structures have been determined by X-ray single crystal analysis. The interactions of the complexes with calf thymus DNA (CT-DNA) have been investigated using UV-vis absorption and viscosity measurements. The results indicate that the complex 1 and complex 2 respectively bind to CT-DNA, and the binding mode of the former is in electrostatic binding or groove mode, while that of the latter is in insertion mode. The complex 2 had better activity to break CT-DNA than complex 1 .
研究领域:
无机化学
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生物无机化学
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药物化学
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分子药理学
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核酸化学
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晶体学
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抗肿瘤药物开发
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产品关联
DOI
高影响因子
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
·
2019
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IF 3.31
Yun Li,Yueqin Li,Nana Wang,Dong Lin,Xiaohui Liu,Yong Yang,Qinwei Gao
Two new nickel (II) triphenylphosphine complexes derived from tridentate aroylhydrazone ligands [H2L1 = 2-hydroxy-3-methoxybenzylidene)benzohydrazone and H2L2 = N′-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazone] and triphenylphosphine were prepared and their molecular structures were determined by single crystal X-ray diffraction analysis. Both nickel(II) complexes showed slightly distorted square planar geometry with one tridentate aroylhydrazone ligand coordinated through ONO donor atoms and one triphenylphosphine ligand coordinated to the nickel center through the phosphorus atom. DNA interaction studies indicated that both complexes possessed higher affinity to herring sperm DNA (HS-DNA) than the corresponding free aroylhydrazone ligand. Molecular docking investigations showed that both complexes could bind to DNA through intercalation of the phenyl rings between adjacent base pairs in the double helix. Meanwhile, bovine serum albumin (BSA) binding studies revealed the complexes could effectively interact with BSA and change the secondary structure of BSA. Further pharmacological evaluations of the synthesized complexes by in vitro antioxidant assays demonstrated high antioxidant activity against NO· and O2˙− radicals. The anticancer activity of each complex was assessed through in vitro cytotoxicity assays (CCK-8 kit) toward A549 and MCF-7 cancer cell and normal L-02 cell lines. Significantly, the Ni(II) complex derived from H2L1 ligand was found to be more effective cytotoxic toward MCF-7cancerous cell with the IC50 value equaled 9.7 μM, which showed potent cytotoxic activity over standard drug cisplatin. AbbreviationsA549human lung carcinoma cellBSAbovine serum albuminCCK-8Cell Counting Kit-8DFTdensity functional theoryDNAdeoxyribonucleic acidDPPH˙2,2-diphenyl-1-picrylhydrazylH2L12-hydroxy-3-methoxybenzylidene)benzohydrazone N′-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazoneH2L2N′-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazoneHOMOhighest occupied molecular orbitalIC50the 50% activityL-02human normal liver cellLOMOlowest unoccupied molecular orbital (LUMO)MCF-7human breast carcinoma cellNO˙nitric oxideO2˙−superoxide anionSODsuperoxide dismutaseCommunicated by Ramaswamy H. Sarma
研究领域:
无机化学
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生物化学
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药理学
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癌症研究
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DOI
PubMed
高影响因子
RSC Advances
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2015
·Vol. 5
·期 19
·14138-14146
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IF 3.84
Jiashan Zhou,Yan Li,Haiqing Dong,Hua Yuan,Tianbin Ren,Yongyong Li
Polymeric catiomers, which can mimic viruses for gene packing and delivery, have received considerable attention as nonviral vectors for gene therapy. Inspired by the critically important role of the sequence of structural units in various biomolecules, including DNA and protein, in this study, we intend to investigate how the monomer sequence of a polymeric catiomer affects its gene packing capacity and delivery efficiency. The well-documented poly(histidine-co-lysine) was chosen as the scaffold for gene carrier. Four reducible polycations (RPCs) based on sequence-regulated peptides monomers were synthesized. Chemical parameters (namely, composition and molecular weight) of four RPCs were controlled at comparable level except for the monomer sequence. All of the RPCs exhibited low cytotoxicity and effective DNA binding ability. However, these RPCs displayed distinct diversity from each other, especially in their ability of binding to DNA, buffering capacity and transfection efficiency. Using 293T cell as the mode, we found that the regulation of the monomer sequence of polycations could significantly affect their properties for gene delivery, with differences of 100 fold. The sequence effect might be correlated with different chain folding as well as physiochemical properties of RPCs/pDNA complexes, providing new insight for designing gene vector with promising prospects in gene therapy.
研究领域:
生物医学工程
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分子生物学
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基因治疗
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产品关联
DOI
高影响因子
Polymers
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2018
·Vol. 10
·期 10
·1080
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IF 2.935
Ju-Hui Zhang,Hui-Zhen Yang,Ji Zhang,Yan-Hong Liu,Xi He,Ya-Ping Xiao,Xiao-Qi Yu
The linking and modification of low molecular weight cationic polymers (oligomers) has become an attracted strategy to construct non-viral gene carriers with good transfection efficiency and much reduced cytotoxicity. In this study, PEI 600 Da was linked by biodegradable bridges containing rigid aromatic rings. The introduction of aromatic rings enhanced the DNA-binding ability of the target polymers and also improved the stability of the formed polymer/DNA complexes. The biodegradable property and resulted DNA release were verified by enzyme stimulated gel electrophoresis experiment. These materials have lower molecular weights compared to PEI 25 kDa, but exhibited higher transfection efficiency, especially in the presence of serum. Flow cytometry and confocal laser scanning microscopy results indicate that the polymers with aromatic rings could induce higher cellular uptake. This strategy for the construction of non-viral gene vectors may be applied as an efficient and promising method for gene delivery.Keywords:non-viral vectors;gene delivery;polyethylenimine;structure–activity relationship
研究领域:
遗传学
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生物技术
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药学
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产品关联
DOI
PubMed
高影响因子
Polysaccharides
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2025
·Vol. 6
·期 3
·60
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IF 5.5
Viktor Korzhikov-Vlakh,Polina Teterina,Nina Gubina,Apollinariia Dzhuzha,Tatiana Tennikova,Evgenia Korzhikova-Vlakh
The synthesis of novel biodegradable polymers as non-viral vectors remains one of the challenging tasks in the field of gene delivery. In this study, the synthesis of the polysaccharide-g-polypeptide copolymers, namely, hyaluronic acid-g-polylysine (HA-g-PLys), using a copper-free strain-promoted azide-alkyne cycloaddition reaction was proposed. For this purpose, hyaluronic acid was modified with dibenzocyclooctyne moieties, and poly-L-lysine with a terminal azido group was obtained using ring-opening polymerization ofN-carboxyanhydride of the corresponding protected amino acid, initiated with the amino group azido-PEG3-amine. Two HA-g-PLys samples with different degrees of grafting were synthesized, and the structures of all modified and synthesized polymers were confirmed using1H NMR and FTIR spectroscopy. The HA-g-PLys samples obtained were able to form nanoparticles in aqueous media due to self-assembly driven by electrostatic interactions. The binding of DNA and model siRNA by copolymers to form polyplexes was analyzed using ethidium bromide, agarose gel electrophoresis, and SybrGreen I assays. The hydrodynamic diameter of polyplexes was ˂300 nm (polydispersity index, PDI ˂ 0.3). The release of a model fluorescently-labeled oligonucleotide in the complex biological medium was significantly higher in the case of HA-g-PLys as compared to that in the case of PLys-based polyplexes. In addition, the cytotoxicity in normal and cancer cells, as well as the ability of HA-g-PLys to facilitate intracellular delivery of anti-GFP siRNA to NIH-3T3/GFP+ cells, were evaluated.
研究领域:
生物化学
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生物技术
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药学
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分子生物学
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高分子科学
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纳米技术
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基因工程
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产品关联
DOI
高影响因子
ANALYTICAL CHEMISTRY
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2014
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IF 5.825
Lihua Zhang,Hua Liu,Yong Shao,Clement Lin,Huan Jia,Gang Chen,Danzhou Yang,Ying Wang
Aptamers, that exist naturally in living cells as functional elements and can switch nonfluorescent natural targets to fluorophores, are very useful in developing highly sensitive and selective biosensors and screening functional agents. This work demonstrates that human telomeric G-quadruplex (HTG) can serve as a potential fluorophore-switching aptamer (FSA) to target a natural isoquinoline alkaloid. We found that, among the G-quadruplexes studied here and the various structurally similar alkaloids including epiberberine (EPI), berberine (BER), palmatine (PAL), jatrorrhizine (JAT), coptisine (COP), worenine (WOR), sanguinarine (SAN), chelerythrine (CHE), and nitidine (NIT), only the HTG DNA, especially with a 5′-TA-3′ residue at the 5′ end of the G-quadruplex tetrad (5′-TAG3(TTAG3)3-3′, TA[Q]) as the minimal sequence, is the most efficient FSA to selectively light up the EPI fluorescence. Compared to the 5′ end flanking sequences, the 3′ end flanking sequences of the tetrad contribute significantly less to the recognition of EPI. The binding affinity of EPI to TA[Q] (Kd = 37 nM) is at least 20 times tighter than those of the other alkaloids. The steady-state absorption, steady-state/time-resolved fluorescence, and NMR studies demonstrate that EPI most likely interact with the 5′ end flanking sequence substructure beyond the core [Q] and the G-quadruplex tetrad in a much more specific manner than the other alkaloids. The highly selective and tight binding of EPI with the FSA and significantly enhanced fluorescence suggest the potential development of a selective EPI sensor (detection limit of 10 nM). More importantly, EPI, as the brightest FSA emitter among the alkaloids, can also serve as an efficient conformation probe for HTG DNA and discriminate the DNA G-quadruplex from the RNA counterpart. Furthermore, EPI can bind stoichiometrically to each G-quadruplex unit of long HTG DNA multimer with the most significant fluorescence enhancement, which has not been achieved by the previously reported probes. Our work suggests the potential use of EPI as a bioimaging probe and a therapeutic DNA binder.
研究领域:
分子生物学
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化学生物学
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纳米技术
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分析化学
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC & MEDICINAL CHEMISTRY
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2013
·
IF 2.903
Ruilong Sheng,Ting Luo,Hui Li,Jingjing Sun,Zhao Wang,Amin Cao
In this work , we have successfully prepared a series of new sterol-based cationic lipids ( 1 – 4 ) via an efficient ‘Click’ chemistry approach. The pDNA binding affinity of these lipids was examined by EB displacement and agarose-gel retardant assay. The average particle sizes and surface charges of the sterol-based cationic lipids/pDNA lipoplexes were analyzed by dynamic laser light scattering instrument (DLS), and the morphologies of the lipoplexes were observed by atomic force microscopy (AFM). The cytotoxicity of the lipids were examined by MTT and LDH assay, and the gene transfection efficiencies of these lipid carriers were investigated by luciferase gene transfection assay in various cell lines. In addition, the intracellular uptake and trafficking/localization behavior of the Cy3-DNA loaded lipoplexes were preliminarily studied by fluorescence microscopy . The results demonstrated that the pDNA loading capacity, lipoplex particle size, zeta potential and morphology of the sterol lipids/pDNA lipoplexes depended largely on the molecular structure factors including sterol-skeletons and headgroups. Furthermore, the sterol-based lipids showed quite different cytotoxicity and gene transfection efficacy in A549 and HeLa cells. Interestingly, it was found that the cholesterol-bearing lipids 1 and 2 showed 7–10 4 times higher transfection capability than their lithocholate-bearing counterparts 3 and 4 in A549 and HeLa cell lines , suggested that the gene transfection capacity strongly relied on the structure of sterol skeletons . Moreover, the study on the structure–activity relationships of these sterol-based cationic lipid gene carriers provided a possible approach for developing low cytotoxic and high efficient lipid gene carriers by selecting suitable sterol hydrophobes and cationic headgroups.
研究领域:
分子生物学
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基因治疗
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药剂学
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DOI
PubMed
高影响因子
JOURNAL OF INORGANIC BIOCHEMISTRY
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2015
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IF 3.444
Lan-mei Chen,Fa Peng,Guo-dong Li,Xin-ming Jie,Kang-rong Cai,Chun Cai,Yu Zhong,Hua Zeng,Wu Li,Zhen Zhang,Jin-can Chen
A new ruthenium methylimidazole complex [Ru(MeIm) 4 ( p -cpip)] 2 + ( Ru1 , p -cpip = 2-(4-chlorophenyl)-1 H-imidazo[4,5-f][1,10]phenanthroline, MeIm = 1-methylimidazole) has been synthesized and characterized. The cellular uptake, in vitro cytotoxicities, cell cycle arrest and apoptosis-inducing mechanism of this Ru(II) complex have been extensively explored by Inductively Coupled Plasma Mass Spectrometry (ICP-MS), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry , Comet assay , inverted fluorescence microscope as well as Western blotting experimental techniques. Notably, Ru1 displayed relatively high cytotoxic activity against lung cancer A549 cells and had high selectivity between tumor and normal cells in comparison with cisplatin . Further studies showed that Ru1 caused cell cycle arrest at G0/G1 phase and induced apoptosis via the mitochondrial pathway, which involved reactive oxygen species (ROS) accumulation, mitochondrial dysfunction and Bcl-2 and caspase correlative family member activation. For providing more information about the possible antitumor mechanism, the in vitro DNA binding studies have been also investigated by different spectrophotometric methods, thermal denaturation and viscosity measurements.
研究领域:
肿瘤学
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药理学
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细胞生物学
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化学
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DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2023
·
IF 13.6
Liubing Kong,Ying Gan,Tianxing Wang,Xianyou Sun,Chiyu Ma,Xinyi Wang,Hao Wan,Ping Wang
Okadaic acid (OA), one of the most widely distributed marine toxins worldwide poses a severe threat to human health. Previous sensing methods for OA detection are usually based on antigen-antibody binding mechanism. However, the drawbacks of antibodies especially the enzyme-labeled antibodies, such as the harsh storage condition and high cost, lead to significant challenges to OA detection in biological samples. To overcome these limitations, a single-stranded DNA binding protein (SSB) coupled aptasensor was developed for OA detection. SSB was incubated on the microplate as a substitute for conventional OA-protein conjugations. Carbon-gold nanoparticles were synthesized and labeled with horseradish peroxidase and thiol-modified aptamers to obtain a capture probe ( [email protected] ) instead of the enzyme-labeled antibody for signal amplification. OA and SSB competed to bind with limited aptamers on [email protected] probes followed by colorimetric assay to obtain the optical signals correlated to OA concentration. To achieve on-site detection, a miniaturized and multichannel absorbance reader (Smart-plate reader) was self-designed with full automation for OA detection. Utilizing the SSB coupled aptasensor and the Smart-plate reader, our approach enables cost-effective and on-site OA sensing with a detection range of 2.5–80 ppb and an ultra-low limit of detection of 0.68 ppb. Moreover, novel OA detection kits based on the SSB coupled aptasensor were prepared which can effectively reduce the cost by 15 times lower than that of commercial ELISA kits. Therefore, the developed platform provides a favorable and promising avenue for marine toxin detection in aquaculture and food safety.
研究领域:
生物技术
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环境科学
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分析化学
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食品安全
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）