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排序方式: 共有225条查询结果,搜索用时 31 毫秒
1.
Siriluk Ratanabunyong Dr. Niran Aeksiri Dr. Saeko Yanaka Dr. Maho Yagi-Utsumi Dr. Koichi Kato Dr. Kiattawee Choowongkomon Dr. Supa Hannongbua 《Chembiochem : a European journal of chemical biology》2021,22(5):915-923
HIV-1 RT is a necessary enzyme for retroviral replication, which is the main target for antiviral therapy against AIDS. Effective anti-HIV-1 RT drugs are divided into two groups; nucleoside inhibitors (NRTI) and non-nucleoside inhibitors (NNRTI), which inhibit DNA polymerase. In this study, new DNA aptamers were isolated as anti-HIV-1 RT inhibitors. The selected DNA aptamer (WT62) presented with high affinity and inhibition against wild-type (WT) HIV-1 RT and gave a KD value of 75.10±0.29 nM and an IC50 value of 84.81±8.54 nM. Moreover, WT62 decreased the DNA polymerase function of K103 N/Y181 C double mutant (KY) HIV-1 RT by around 80 %. Furthermore, the ITC results showed that this aptamer has small binding enthalpies with both WT and KY HIV-1 RTs through which the complex might form a hydrophobic interaction or noncovalent bonding. The NMR result also suggested that the WT62 aptamer could bind with both WT and KY mutant HIV-1 RTs at the connection domain. 相似文献
2.
Dr. Masanobu Nagano Takumi Oguro Ryo Sawada Dr. Toru Yoshitomi Prof. Keitaro Yoshimoto 《Chembiochem : a European journal of chemical biology》2021,22(23):3341-3347
Dysregulation of tumor necrosis factor-α (TNFα), a pro-inflammatory cytokine, causes several diseases, making it an important therapeutic target. Here, we identified a novel DNA aptamer against human TNFα using in vitro selection, which included a high exclusion pressure process against non-binding and weak binders through microbead-assisted capillary electrophoresis (MACE) in only three rounds. Among the 15 most enriched aptamers, Apt14 exhibited the highest inhibitory activity for the interaction between TNFα and its cognate receptor in mouse L929 cells. For further improving the bioactivity of the aptamer, dimerization programed by hybridization was evaluated, resulting in the Apt14 dimer exhibited a twofold higher binding affinity and stronger inhibition compared to the monomer counterpart. Rapid identification of bioactive aptamers using MACE in combination with facile dimerization by hybridization accelerates the discovery of novel bioactive aptamers, paving the way toward replacing current monoclonal antibody therapy with the less expensive and non-immunogenic aptamer therapy. 相似文献
3.
Lu Yang Dr. Mingwei Liang Dr. Cheng Cui Xiaowei Li Long Li Xiaoshu Pan Hoda Safari Yazd Dr. Min Hong Prof. Jianrong Lu Prof. Y. Charles Cao Prof. Weihong Tan 《Chembiochem : a European journal of chemical biology》2021,22(4):754-759
Functional nucleic acids (FNAs) are garnering tremendous interest owing to their high modularity and unique bioactivity. Three-dimensional FNAs have been developed to overcome the issues of nuclease degradation and limited cell uptake. We have developed a new facile approach to the synthesis of multiple three-dimensional FNA nanostructures by harnessing photo-polymerization-induced self-assembly. Sgc8 aptamer and CpG oligonucleotide were modified as macro chain-transfer reagents to mediate in situ polymerization and self-assembly. Diverse structures, including micelles, rods, and short worms, afford these two FNAs afford these two FNAs with higher nuclease resistance in serum serum, greater cellular uptake efficiency, and increased bioactivity. 相似文献
4.
5.
Andrey A. Buglak Alexey V. Samokhvalov Anatoly V. Zherdev Boris B. Dzantiev 《International journal of molecular sciences》2020,21(22)
Aptamers are nucleic acid analogues of antibodies with high affinity to different targets, such as cells, viruses, proteins, inorganic materials, and coenzymes. Empirical approaches allow the design of in vitro aptamers that bind particularly to a target molecule with high affinity and selectivity. Theoretical methods allow significant expansion of the possibilities of aptamer design. In this study, we review theoretical and joint theoretical-experimental studies dedicated to aptamer design and modeling. We consider aptamers with different targets, such as proteins, antibiotics, organophosphates, nucleobases, amino acids, and drugs. During nucleic acid modeling and in silico design, a full set of in silico methods can be applied, such as docking, molecular dynamics (MD), and statistical analysis. The typical modeling workflow starts with structure prediction. Then, docking of target and aptamer is performed. Next, MD simulations are performed, which allows for an evaluation of the stability of aptamer/ligand complexes and determination of the binding energies with higher accuracy. Then, aptamer/ligand interactions are analyzed, and mutations of studied aptamers made. Subsequently, the whole procedure of molecular modeling can be reiterated. Thus, the interactions between aptamers and their ligands are complex and difficult to understand using only experimental approaches. Docking and MD are irreplaceable when aptamers are studied in silico. 相似文献
6.
Woohyun J. Moon Prof. Dr. Juewen Liu 《Chembiochem : a European journal of chemical biology》2020,21(3):401-407
It has been proposed that Mg2+ and Fe2+ are very similar in interacting with ribozymes and some protein-based enzymes, but their activities with DNAzymes have yet to be studied. Here, the activity of Fe2+ as cofactor for a few RNA-cleaving DNAzymes is investigated. 17E is a well-studied DNAzyme that is active in the presence of many different divalent metal ions; it is highly active with Fe2+ with an apparent Kd of 29.7±2.3 μm and a kobs of 1.12±0.11 min−1 in the presence of 1 mm Fe2+ at pH 7.5. Fe2+ has 21-fold higher activity than Mg2+. Six different DNAzymes are then tested, and only the DNAzymes active with Mg2+ (17E, 8–17, and E5) are active with Fe2+. Fe2+ has 25 and one- to twofold higher activity than Mg2+ for the 8–17 and E5 DNAzymes, respectively. In pH>7 buffer and in presence of air, 1 mm Fe2+ results in a nonspecific degradation of the DNA strand due to reactive oxygen species (ROS). Cleavage reactions in anoxic environment and antioxidant ascorbate can be used to overcome the effect of oxidation. The findings provide insights for potential DNAzyme catalysis in the early Earth, and they further support the similarity between Mg2+ and Fe2+ in enzyme catalysis. 相似文献
7.
Capt. Courtney Kiggins Austin Skinner Prof. Marino J. E. Resendiz 《Chembiochem : a European journal of chemical biology》2020,21(9):1347-1355
Aptamers are attractive constructs due to their high affinity/selectivity towards a target. Here 7,8-dihydro-8-oxoguanosine (8-oxoG) has been used, due in part to its unique H-bonding capabilities (Watson–Crick or Hoogsteen), to expand the “RNA alphabet”. Its impact on the theophylline RNA aptamer was explored by modifying its binding pocket at positions G11, G25, or G26. Structural probing, with RNases A and T1, showed that modification at G11 leads to a drastic structural change, whereas the G25-/G26-modified analogues exhibited cleavage patterns similar to that of the canonical construct. The recognition properties towards three xanthine derivatives were then explored through thermophoresis. Modifying the aptamer at position G11 led to binding inhibition. Modification at G25, however, changed the selectivity towards theobromine (Kd≈160 μm ), with a poor affinity for theophylline (Kd>1.5 mm ) being observed. Overall, 8-oxoG can have an impact on the structures of aptamers in a position-dependent manner, leading to altered target selectivity. 相似文献
8.
Krisztina Percze Dr. Tamás Mészáros 《Chembiochem : a European journal of chemical biology》2020,21(20):2939-2944
One of the pivotal steps in aptamer selection is the amplification of target-specific oligonucleotides by thermophilic DNA polymerases; it can be a challenging task if nucleic acids possessing modified nucleotides are to be amplified. Hence, the identification of compatible DNA polymerase and modified nucleotide pairs is necessary for effective selection of aptamers with unnatural nucleotides. We present an in-depth study of using 5-indolyl-AA-dUTP (TAdUTP) to generate oligonucleotide libraries for aptamer selection. We found that, among the eight studied DNA polymerases, only Vent(exo-) and KOD XL are capable of adapting TAdUTP, and that replacing dTTP did not have a significant effect on the productivity of KOD XL. We demonstrated that water-in-oil emulsion PCR is suitable for the generation of aptamer libraries of modified nucleotides. Finally, high-throughput sequence analysis showed that neither the error rate nor the PCR bias was significantly affected by using TAdUTP. In summary, we propose that KOD XL and TAdUTP could be effectively used for aptamer selection without distorting the sequence space of random oligonucleotide libraries. 相似文献
9.
10.
Dr. Yibo Liu Prof. Juewen Liu 《Chembiochem : a European journal of chemical biology》2023,24(2):e202200564
Uric acid is the end-product of purine metabolism in humans and an important biomarker for many diseases. To achieve the detection of uric acid without using enzymes, we previously selected a DNA aptamer for uric acid with a Kd of 1 μM but the aptamer required multiple Na+ ions for binding. Saturated binding was achieved with around 700 mM Na+ and the binding at the physiological condition was much weaker. In this work, a new selection was performed by alternating Mg2+-containing buffers with Na+ and Li+. After 13 rounds of selection, a new aptamer sequence named UA-Mg-1 was obtained. Isothermal titration calorimetry confirmed aptamer binding in both selection buffers, and the Kd was around 8 μM. The binding of UA-Mg-1 to UA required only Mg2+. This is an indicator of successful switching of metal dependency via the salt-toggled selection method. The UA-Mg-1 aptamer was engineered into a fluorescent biosensor based on the strand-displacement assay with a limit of detection of 0.5 μM uric acid in the selection buffer. Finally, comparison with the previously reported Na+-dependent aptamer and a xanthine/uric acid riboswitch was also made. 相似文献