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1

Zhang, Li, and John C. Chaput. "In Vitro Selection of an ATP-Binding TNA Aptamer." Molecules 25, no. 18 (September 13, 2020): 4194. http://dx.doi.org/10.3390/molecules25184194.

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Recent advances in polymerase engineering have made it possible to isolate aptamers from libraries of synthetic genetic polymers (XNAs) with backbone structures that are distinct from those found in nature. However, nearly all of the XNA aptamers produced thus far have been generated against protein targets, raising significant questions about the ability of XNA aptamers to recognize small molecule targets. Here, we report the evolution of an ATP-binding aptamer composed entirely of α-L-threose nucleic acid (TNA). A chemically synthesized version of the best aptamer sequence shows high affinity to ATP and strong specificity against other naturally occurring ribonucleotide triphosphates. Unlike its DNA and RNA counterparts that are susceptible to nuclease digestion, the ATP-binding TNA aptamer exhibits high biological stability against hydrolytic enzymes that rapidly degrade DNA and RNA. Based on these findings, we suggest that TNA aptamers could find widespread use as molecular recognition elements in diagnostic and therapeutic applications that require high biological stability.
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2

Esawi, Ezaldeen, Walhan Alshaer, Ismail Sami Mahmoud, Dana A. Alqudah, Bilal Azab, and Abdalla Awidi. "Aptamer-Aptamer Chimera for Targeted Delivery and ATP-Responsive Release of Doxorubicin into Cancer Cells." International Journal of Molecular Sciences 22, no. 23 (November 30, 2021): 12940. http://dx.doi.org/10.3390/ijms222312940.

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Aptamers offer a great opportunity to develop innovative drug delivery systems that can deliver cargos specifically into targeted cells. In this study, a chimera consisting of two aptamers was developed to deliver doxorubicin into cancer cells and release the drug in cytoplasm in response to adenosine-5′-triphosphate (ATP) binding. The chimera was composed of the AS1411 anti-nucleolin aptamer for cancer cell targeting and the ATP aptamer for loading and triggering the release of doxorubicin in cells. The chimera was first produced by hybridizing the ATP aptamer with its complementary DNA sequence, which is linked with the AS1411 aptamer via a poly-thymine linker. Doxorubicin was then loaded inside the hybridized DNA region of the chimera. Our results show that the AS1411–ATP aptamer chimera was able to release loaded doxorubicin in cells in response to ATP. In addition, selective uptake of the chimera into cancer cells was demonstrated using flow cytometry. Furthermore, confocal laser scanning microscopy showed the successful delivery of the doxorubicin loaded in chimeras to the nuclei of targeted cells. Moreover, the doxorubicin-loaded chimeras effectively inhibited the growth of cancer cell lines and reduced the cytotoxic effect on the normal cells. Overall, the results of this study show that the AS1411–ATP aptamer chimera could be used as an innovative approach for the selective delivery of doxorubicin to cancer cells, which may improve the therapeutic potency and decrease the off-target cytotoxicity of doxorubicin.
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3

Xie, Ya-chen, Leif A. Eriksson, and Ru-bo Zhang. "Molecular dynamics study of the recognition of ATP by nucleic acid aptamers." Nucleic Acids Research 48, no. 12 (May 22, 2020): 6471–80. http://dx.doi.org/10.1093/nar/gkaa428.

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Abstract Despite their great success in recognizing small molecules in vitro, nucleic acid aptamers are rarely used in clinical settings. This is partially due to the lack of structure-based mechanistic information. In this work, atomistic molecular dynamics simulations are used to study the static and dynamic supramolecular structures relevant to the process of the wild-type (wt) nucleic acid aptamer recognition and binding of ATP. The effects brought about by mutation of key residues in the recognition site are also explored. The simulations reveal that the aptamer displays a high degree of rigidity and is structurally very little affected by the binding of ATP. Interaction energy decomposition shows that dispersion forces from π-stacking between ATP and the G6 and A23 nucleobases in the aptamer binding site plays a more important role in stabilizing the supramolecular complex, compared to hydrogen-bond interaction between ATP and G22. Moreover, metadynamics simulations show that during the association process, water molecules act as essential bridges connecting ATP with G22, which favors the dynamic stability of the complex. The calculations carried out on three mutated aptamer structures confirm the crucial role of the hydrogen bonds and π-stacking interactions for the binding affinity of the ATP nucleic acid aptamer.
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4

Zhang, Zijie, and Juewen Liu. "An engineered one-site aptamer with higher sensitivity for label-free detection of adenosine on graphene oxide." Canadian Journal of Chemistry 96, no. 11 (November 2018): 957–63. http://dx.doi.org/10.1139/cjc-2017-0601.

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The 27-nucleotide DNA aptamer for adenosine and ATP, originally selected by the Szostak lab in 1995, has been a very popular model system for biosensor development. This unique aptamer has two target binding sites, and we recently showed that it is possible to remove either site while the other one still retains binding. From an analytical perspective, tuning the number of binding sites has important implications in modulating sensitivity of the resulting biosensors. In this work, we report that the engineered one-site aptamer showed excellent signaling properties with a 2.6-fold stronger signal intensity and also a 4.2-fold increased detection limit compared with the wild-type two-site aptamer. The aptamer has a hairpin structure, and the length of the hairpin stem was systematically varied for the one-site aptamers. Isothermal titration calorimetry and a label-free fluorescence signaling method with graphene oxide and SYBR Green I were respectively used to evaluate binding and sensor performance. Although longer stemmed aptamers produced better adenosine binding affinity, the signaling was quite independent of the stem length as long as more than three base pairs were left. This was explained by the higher affinity of binding to GO by the longer aptamers, cancelling out the higher affinity for adenosine binding. This work further confirms the analytical applications of such one-site adenosine aptamers, which are potentially useful for improved ATP imaging and for developing new biosensors.
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5

Mulyani, Rahmaniar, Nida Yumna, Iman Permana Maksum, Toto Subroto, and Yeni Wahyuni Hartati. "Optimization of Aptamer-Based Electrochemical Biosensor for ATP Detection Using Screen-Printed Carbon Electrode/Gold Nanoparticles (SPCE/AuNP)." Indonesian Journal of Chemistry 22, no. 5 (September 28, 2022): 1256. http://dx.doi.org/10.22146/ijc.72820.

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Electrochemical biosensors are used to detect adenosine triphosphate (ATP) levels, which are involved in a variety of biological processes, such as regulating cellular metabolism and biochemical pathways. Therefore, this research aims to develop an aptamer-based electrochemical biosensor with Screen Printed Carbon Electrode/gold nanoparticles (SPCE/AuNP) and collect data as well as information related to ATP detection. The modification of SPCE with AuNP increased the analyte’s binding sensitivity and biocompatibility. The aptamer was selected based on its excellent bioreceptor characteristics. Furthermore, aptamer–SH (F1) and aptamer-NH2 (F2) were immobilized on the SPCE/AuNP surface, which had been characterized using SEM, EIS, and DPV. Also, the ATP-binding aptamers were electrochemically characterized using the K3[Fe(CN)6] redox system and Differential Pulse Voltammetry (DPV). According to the optimization results using the Box-Behnken experimental design, the ideal conditions obtained from the factors influencing the experiment were the F1 concentration and incubation time of 4 µM and 24 h, respectively, as well as F1/F2/ATP incubation time of 7.5 min. Meanwhile, for the range of 0.1 to 100 µM, the detection (LoD) and quantification (LoQ) limits were 7.43 and 24.78 µM, respectively. Therefore, this aptasensor method can be used to measure ATP levels in real samples.
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6

Wulf, Verena, and Itamar Willner. "Nucleoapzymes: catalyst-aptamer conjugates as enzyme-mimicking structures." Emerging Topics in Life Sciences 3, no. 5 (August 23, 2019): 493–99. http://dx.doi.org/10.1042/etls20190054.

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The conjugation of catalytic sites to sequence-specific, ligand-binding nucleic acid aptamers yields functional catalytic ensembles mimicking the catalytic/binding properties of native enzymes. These catalyst-aptamer conjugates termed ‘nucleoapzymes’ reveal structural diversity, and thus, vary in their catalytic activity, due to the different modes of conjugation of the catalytic units to the nucleic acid aptamer scaffold. The concept of nucleoapzymes is introduced with the assembly of a set of catalysts consisting of the hemin/G-quadruplex DNAzyme (hGQ) conjugated to the dopamine aptamer. The nucleoapzymes catalyze the oxidation of dopamine by H2O2 to yield aminochrome. The catalytic processes are controlled by the structures of the nucleoapzymes, and chiroselective oxidation of l-DOPA and d-DOPA by the nucleoapzymes is demonstrated. In addition, the conjugation of a Fe(III)-terpyridine complex to the dopamine aptamer and of a bis-Zn(II)-pyridyl-salen-type complex to the ATP-aptamer yields hybrid nucleoapzymes (conjugates where the catalytic site is not a biomolecule) that catalyze the oxidation of dopamine to aminochrome by H2O2 and the hydrolysis of ATP to ADP, respectively. Variable, structure-controlled catalytic activities of the different nucleoapzymes are demonstrated. Molecular dynamic simulations are applied to rationalize the structure-catalytic function relationships of the different nucleoapzymes. The challenges and perspectives of the research field are discussed.
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7

Heddinga, Marius H., and Jens Müller. "Incorporation of a metal-mediated base pair into an ATP aptamer – using silver(I) ions to modulate aptamer function." Beilstein Journal of Organic Chemistry 16 (November 25, 2020): 2870–79. http://dx.doi.org/10.3762/bjoc.16.236.

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For the first time, a metal-mediated base pair has been used to modulate the affinity of an aptamer towards its target. In particular, two artificial imidazole 2’-deoxyribonucleosides (Im) were incorporated into various positions of an established ATP-binding aptamer (ATP, adenosine triphosphate), resulting in the formation of three aptamer derivatives bearing Im:Im mispairs with a reduced ATP affinity. A fluorescence spectroscopy assay and a binding assay with immobilized ATP were used to evaluate the aptamer derivatives. Upon the addition of one Ag(I) ion per mispair, stabilizing Im–Ag(I)–Im base pairs were formed. As a result, the affinity of the aptamer derivative towards ATP is restored again. The silver(I)-mediated base-pair formation was particularly suitable to modulate the aptamer function when the Im:Im mispairs (and hence the resulting metal-mediated base pairs) were located close to the ATP-binding pocket of the aptamer. Being able to trigger the aptamer function opens new possibilities for applications of oligonucleotides.
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8

Nandimandalam, Manasa, Francesca Costantini, Nicola Lovecchio, Lorenzo Iannascoli, Augusto Nascetti, Giampiero de Cesare, Domenico Caputo, and Cesare Manetti. "Split Aptamers Immobilized on Polymer Brushes Integrated in a Lab-on-Chip System Based on an Array of Amorphous Silicon Photosensors: A Novel Sensor Assay." Materials 14, no. 23 (November 26, 2021): 7210. http://dx.doi.org/10.3390/ma14237210.

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Innovative materials for the integration of aptamers in Lab-on-Chip systems are important for the development of miniaturized portable devices in the field of health-care and diagnostics. Herein we highlight a general method to tailor an aptamer sequence in two subunits that are randomly immobilized into a layer of polymer brushes grown on the internal surface of microfluidic channels, optically aligned with an array of amorphous silicon photosensors for the detection of fluorescence. Our approach relies on the use of split aptamer sequences maintaining their binding affinity to the target molecule. After binding the target molecule, the fragments, separately immobilized to the brush layer, form an assembled structure that in presence of a “light switching” complex [Ru(phen)2(dppz)]2+, emit a fluorescent signal detected by the photosensors positioned underneath. The fluorescent intensity is proportional to the concentration of the target molecule. As proof of principle, we selected fragments derived from an aptamer sequence with binding affinity towards ATP. Using this assay, a limit of detection down to 0.9 µM ATP has been achieved. The sensitivity is compared with an assay where the original aptamer sequence is used. The possibility to re-use both the aptamer assays for several times is demonstrated.
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9

Biniuri, Yonatan, Bauke Albada, and Itamar Willner. "Probing ATP/ATP-Aptamer or ATP-Aptamer Mutant Complexes by Microscale Thermophoresis and Molecular Dynamics Simulations: Discovery of an ATP-Aptamer Sequence of Superior Binding Properties." Journal of Physical Chemistry B 122, no. 39 (September 6, 2018): 9102–9. http://dx.doi.org/10.1021/acs.jpcb.8b06802.

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10

Xu, Peipei, and Guangfu Liao. "A Novel Fluorescent Biosensor for Adenosine Triphosphate Detection Based on a Metal–Organic Framework Coating Polydopamine Layer." Materials 11, no. 9 (September 5, 2018): 1616. http://dx.doi.org/10.3390/ma11091616.

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In this work, a novel and sensitive fluorescent biosensor based on polydopamine coated Zr-based metal–organic framework (PDA/UiO-66) is presented for adenosine triphosphate (ATP) detection. This PDA/UiO-66 nanoparticle which holds a great potential to be excellent fluorescence quencher can protect the 6-carboxyfluorescein (FAM)-labeled probe from cleaved by DNase I dispersed in solution and the flurescence of labeled FAM is quenched. When ATP molecules exist, aptamers on the PDA/UiO-66 nanoparticles can hybridize with ATP molecule to form complex structure that will be desorbed from the PDA/UiO-66 and digested by DNase I. After that, the released ATP molecule can react with another aptamer on the PDA/UiO-66 complexes, then restarts a new cycle. Herein, the excellent strong fluorescence quenching ability and uploading more amount of aptamer probes of PDA/UiO-66 composites make them efficient biosensors, leading to a high sensitivity with detection limit of 35 nM. Compared with ATP detection directly by UiO-66-based method, the LOD is about 5.7 times higher with PDA/UiO-66 nanoparticle. Moreover, the enhanced biocompatibility and bioactivity with PDA layer of the composites render a proposed strategy for clinical diagnosis field of detecting small biological molecules in vivo in the future.
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11

Debiais, Mégane, Amandine Lelievre, Michael Smietana, and Sabine Müller. "Splitting aptamers and nucleic acid enzymes for the development of advanced biosensors." Nucleic Acids Research 48, no. 7 (February 29, 2020): 3400–3422. http://dx.doi.org/10.1093/nar/gkaa132.

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Abstract In analogy to split-protein systems, which rely on the appropriate fragmentation of protein domains, split aptamers made of two or more short nucleic acid strands have emerged as novel tools in biosensor set-ups. The concept relies on dissecting an aptamer into a series of two or more independent fragments, able to assemble in the presence of a specific target. The stability of the assembled structure can further be enhanced by functionalities that upon folding would lead to covalent end-joining of the fragments. To date, only a few aptamers have been split successfully, and application of split aptamers in biosensing approaches remains as promising as it is challenging. Further improving the stability of split aptamer target complexes and with that the sensitivity as well as efficient working modes are important tasks. Here we review functional nucleic acid assemblies that are derived from aptamers and ribozymes/DNAzymes. We focus on the thrombin, the adenosine/ATP and the cocaine split aptamers as the three most studied DNA split systems and on split DNAzyme assemblies. Furthermore, we extend the subject into split light up RNA aptamers used as mimics of the green fluorescent protein (GFP), and split ribozymes.
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12

Zhang, Siqi, Kun Wang, Jiali Li, Zhenyu Li, and Ting Sun. "Highly efficient colorimetric detection of ATP utilizing a split aptamer target binding strategy and superior catalytic activity of graphene oxide–platinum/gold nanoparticles." RSC Advances 5, no. 92 (2015): 75746–52. http://dx.doi.org/10.1039/c5ra13550h.

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The specific binding of ATP and its aptamer linked the split aptamer-modified GO/PDDA/PtAuNPs and magnetic beads together. Using magnetic separation, TMB was catalyzed into a colored product by nanocomposites, which enabled rapid detection of ATP.
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13

Zhao, Jing, Satoshi Katsube, Junpei Yamamoto, Kazuhiko Yamasaki, Makoto Miyagishi, and Shigenori Iwai. "Analysis of ATP and AMP binding to a DNA aptamer and its imidazole-tethered derivatives by surface plasmon resonance." Analyst 140, no. 17 (2015): 5881–84. http://dx.doi.org/10.1039/c5an01347j.

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14

Schäfer, Thomas, and Veli Cengiz Özalp. "DNA-aptamer gating membranes." Chemical Communications 51, no. 25 (2015): 5471–74. http://dx.doi.org/10.1039/c4cc09660f.

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15

Mashima, T., A. Matsugami, S. Nakano, M. Inoue, M. Fukuda, T. Morii, and M. Katahira. "Structural analysis of ribonucleopeptide aptamer against ATP." Nucleic Acids Symposium Series 53, no. 1 (September 1, 2009): 267–68. http://dx.doi.org/10.1093/nass/nrp134.

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16

Park, Yoojin, Duangrat Nim-anussornkul, Tirayut Vilaivan, Takashi Morii, and Byeang Hyean Kim. "Facile conversion of ATP-binding RNA aptamer to quencher-free molecular aptamer beacon." Bioorganic & Medicinal Chemistry Letters 28, no. 2 (January 2018): 77–80. http://dx.doi.org/10.1016/j.bmcl.2017.12.008.

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Feng, Yanting, Lei He, Ling Wang, Rijian Mo, Chunxia Zhou, Pengzhi Hong, and Chengyong Li. "Detection of Aflatoxin B1 Based on a Porous Anodized Aluminum Membrane Combined with Surface-Enhanced Raman Scattering Spectroscopy." Nanomaterials 10, no. 5 (May 24, 2020): 1000. http://dx.doi.org/10.3390/nano10051000.

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An Aflatoxin B1 (AFB1) biosensor was fabricated via an Ag nanoparticles assembly on the surface of a porous anodized aluminum (PAA) membrane. First, the Raman reporter 4-Aminothiophenol (4-ATP) and DNA (partially complementary to AFB1 aptamer) were attached to the surface of Ag nanoparticles (AgNPs) by chemical bonding to form a 4-ATP-AgNPs-DNA complex. Similarly, the surface of a PAA membrane was functionalized with an AFB1 aptamer. Then, the PAA surface was functionalized with 4-ATP-AgNPs-DNA through base complementary pairing to form AgNPs-PAA sensor with a strong Raman signal. When AFB1 was added, AgNPs would be detached from the PAA surface because of the specific binding between AFB1 and the aptamer, resulting in a reduction in Raman signals. The detection limit of the proposed biosensor is 0.009 ng/mL in actual walnut and the linear range is 0.01–10 ng/mL. The sensor has good selectivity and repeatability; it can be applied to the rapid qualitative and quantitative detection of AFB1.
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18

Zhu, Xiaoli, Bin Zhang, Zonghuang Ye, Hai Shi, Yalan Shen, and Genxi Li. "An ATP-responsive smart gate fabricated with a graphene oxide–aptamer–nanochannel architecture." Chemical Communications 51, no. 4 (2015): 640–43. http://dx.doi.org/10.1039/c4cc07990f.

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19

Biniuri, Yonatan, Guo-Feng Luo, Michael Fadeev, Verena Wulf, and Itamar Willner. "Redox-Switchable Binding Properties of the ATP–Aptamer." Journal of the American Chemical Society 141, no. 39 (September 3, 2019): 15567–76. http://dx.doi.org/10.1021/jacs.9b06256.

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20

Sitaula, Sarita, Shirmir D. Branch, and Mehnaaz F. Ali. "GOx signaling triggered by aptamer-based ATP detection." Chemical Communications 48, no. 74 (2012): 9284. http://dx.doi.org/10.1039/c2cc34279k.

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21

Yao, Wu, Lun Wang, Haiyan Wang, Xiaolei Zhang, and Ling Li. "An aptamer-based electrochemiluminescent biosensor for ATP detection." Biosensors and Bioelectronics 24, no. 11 (July 2009): 3269–74. http://dx.doi.org/10.1016/j.bios.2009.04.016.

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22

Huizenga, David E., and Jack W. Szostak. "A DNA Aptamer That Binds Adenosine and ATP." Biochemistry 34, no. 2 (January 1995): 656–65. http://dx.doi.org/10.1021/bi00002a033.

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23

Ren, L. j., X. Wei, X. x. Hang, P. Zhang, J. t. Zhang, Q. f. Zhang, and L. y. Jiang. "Optimization of fluorescent aptamer sensor for ATP detection." Journal of Physics: Conference Series 1209 (April 2019): 012011. http://dx.doi.org/10.1088/1742-6596/1209/1/012011.

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24

Liao, Wei-Ching, Sivan Lilienthal, Jason S. Kahn, Marianna Riutin, Yang Sung Sohn, Rachel Nechushtai, and Itamar Willner. "pH- and ligand-induced release of loads from DNA–acrylamide hydrogel microcapsules." Chemical Science 8, no. 5 (2017): 3362–73. http://dx.doi.org/10.1039/c6sc04770j.

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A generic method of preparing stimuli-responsive substrate-loaded hydrogel microcapsules, composed of polyacrylamide chains cross-linked by nucleic acids, has been described. The triggered release of loads from the microcapsules proceeds via either the formation of an ATP aptamer or a cocaine aptamer, or the pH-induced generation of i-motif structures.
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Li, Yapiao, Hao Yu, and Qiang Zhao. "Aptamer fluorescence anisotropy assays for detection of aflatoxin B1 and adenosine triphosphate using antibody to amplify signal change." RSC Advances 12, no. 12 (2022): 7464–68. http://dx.doi.org/10.1039/d2ra00843b.

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Hu, Dongyue, Shusen Xiao, Qiaqia Guo, Rongrong Yue, Demin Geng, and Debin Ji. "Luminescence method for detection of aflatoxin B1 using ATP-releasing nucleotides." RSC Advances 11, no. 39 (2021): 24027–31. http://dx.doi.org/10.1039/d1ra03870b.

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Li, Yuqing, Biwu Liu, Zhicheng Huang, and Juewen Liu. "Engineering base-excised aptamers for highly specific recognition of adenosine." Chemical Science 11, no. 10 (2020): 2735–43. http://dx.doi.org/10.1039/d0sc00086h.

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Wang, Ya-Xin, Dong-Xia Wang, Jia-Yi Ma, Jing Wang, Yi-Chen Du, and De-Ming Kong. "DNA nanolantern-based split aptamer probes for in situ ATP imaging in living cells and lighting up mitochondria." Analyst 146, no. 8 (2021): 2600–2608. http://dx.doi.org/10.1039/d1an00275a.

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Wang, Wei, Chen Chen, Xiaoxiao Li, Shiying Wang, and Xiliang Luo. "A bioresponsive controlled-release bioassay based on aptamer-gated Au nanocages and its application in living cells." Chemical Communications 51, no. 44 (2015): 9109–12. http://dx.doi.org/10.1039/c5cc02452h.

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HUANG, Z. "Evolution of aptamers with a new specificity and new secondary structures from an ATP aptamer." RNA 9, no. 12 (December 1, 2003): 1456–63. http://dx.doi.org/10.1261/rna.5990203.

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Li, Yuqing, and Juewen Liu. "Correction: Aptamer-based strategies for recognizing adenine, adenosine, ATP and related compounds." Analyst 146, no. 4 (2021): 1472–73. http://dx.doi.org/10.1039/d0an90126a.

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Burcoglu-Oral, Arsinur D. "The Biologic Meaning of the Structural Components of Defibrotide (DF) in the Setting of HIV Disease with Refractory Herpes, Candida, Cryptosporidium Diarrhea and Multi-Organ Failure Against the Background of Down-Regulation of Cellular Immunity, Autocrine Upregulation of Inflammatory Cytokines of TNF-Alpha, IL2, IL1, IL6 and Dysregulation of cAMP/cGMP Protein Kinase A/C Signalling." Blood 110, no. 11 (November 16, 2007): 3865. http://dx.doi.org/10.1182/blood.v110.11.3865.3865.

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Abstract Production of DF from native mammalian DNA involves heat controlled depolimerization of polymerized nucleic acids as a function of hyperchromicity measured at wavelengths of 260–280 nm as the ratio of Optical Density (OD) in (disorderly phase)/(OD) in (orderly phase). In double helix DNA this rearrangement can be of the order of 100%. DF is defined to represent a hyperchromicity ratio around 15%. Its structural formula is static: P1-5, (dAp)12–24, (dGp) 10–20, (dTp)13–26, (dCp)10–20. ASH Abstract #4086, 2004 reported sequence identities of the fragments at MW </=560 Da (the calculated MW of alkali Na-salt of ATP), using Reversed Phase- HPLC and (MALDI-TOF) (Oral, Lewis),to represent the capability of DF for 15% molecular rearrangement to include but not limited to: dC, dA, G, dGMP, AMP, dTTP, CTP, ATP, dGTP, CMP, cGMP, dAMP. 4 aptamers were sequenced from the PCR product of the double-stranded Defibrotide precursor (Schroer). We have analyzed Aptamer #4 of the sequence 5′ggtggtggttgtggt against the gag/pol region of HIV, and found 3 homology sites. Translation of the aptamer region in gag is a peptide “PEPTA”, and a pol gene fragment translates the same DNA sequence into TRANS. There is a conserved hairpin in the gag/pol region, just before the aptamer #4 homology. Other homologies of Aptamer #4 include but are not limited to the self-replicating portion of mitochondrial DNA (G.Gorilla, H.Sapiens), Candida tropicalis, but not Herpes, etc. T he reproducibility of these sequences in different batches of DF are still under study, and to be reported at the time of the ASH meeting. DF’s mechanism of efficacy as a dose dependent modulator of 2nd messengers, however, are based on a more universally reported data. Highlighted in the literature are the HIV induced loss of bi-directional phosphorilation between Gs GTP/Gs GDP in favor of unidirectional continuous activation of adenylate cyclase (AC) by Gs GTP and secondary uninhibited upregulation of cAMP production. This leads to a known intracellular imbalance between cAMP/cGMP favoring viral replication. Also known are Beta Adrenoreceptor coupling to AC by Gs GTP, and secondary upregulation of autocrine production of inflammatory cytokines of TNF-Alpha, IL6, IL2, IL1, as well as micelle and spore formation of Candida Albicans (Sabie). Similarly, HSV-1 Alpha0 Promoter isknown to contain a putative cAMP responsive element (CRE) via activating transcriptor protein ATP/cAMP CRE binding protein CREB, NF-kB via CA ((Danaher). Reported are upregulation of cAMP, ATP, NADH, gluthathione, 2–3 DPG, NADP /NADPH, and AC by DF, albeit as static events. We will report on an in-vivo dose system aiming at resetting the broken feedback loops of bi-directional phosphorilation reactions as a common denominator for DF’s mechanism of efficacy. The patient data dose-stratified from 40mg/kg/day to 300mg/kg/day using either approach are to be detailed at the time of the upcoming ASH meetings.
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Munzar, Jeffrey D., Andy Ng, Mario Corrado, and David Juncker. "Complementary oligonucleotides regulate induced fit ligand binding in duplexed aptamers." Chemical Science 8, no. 3 (2017): 2251–56. http://dx.doi.org/10.1039/c6sc03993f.

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Le, Huynh-Nhu, Xiao-Qin Jiang, Min Zhang, and Bang-Ce Ye. "Label-free fluorescent assay of ATP based on an aptamer-assisted light-up of Hoechst dyes." Anal. Methods 6, no. 7 (2014): 2028–30. http://dx.doi.org/10.1039/c3ay42187b.

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Jing, Cheng, Haohan Chen, Rongfeng Cai, Yaping Tian, and Nandi Zhou. "An electrochemical aptasensor for ATP based on a configuration-switchable tetrahedral DNA nanostructure." Analytical Methods 12, no. 25 (2020): 3285–89. http://dx.doi.org/10.1039/d0ay00431f.

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36

Li, Xin, Ying Peng, Yaqin Chai, Ruo Yuan, and Yun Xiang. "A target responsive aptamer machine for label-free and sensitive non-enzymatic recycling amplification detection of ATP." Chemical Communications 52, no. 18 (2016): 3673–76. http://dx.doi.org/10.1039/c6cc00110f.

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Jiang, Yanan, Wenjie Ma, Wenliang Ji, Huan Wei, and Lanqun Mao. "Aptamer superstructure-based electrochemical biosensor for sensitive detection of ATP in rat brain with in vivo microdialysis." Analyst 144, no. 5 (2019): 1711–17. http://dx.doi.org/10.1039/c8an02077a.

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38

Wu, Chao, Shengyuan Yang, Zhaoyang Wu, Guoli Shen, and Ruqin Yu. "Split Aptamer-Based Liquid Crystal Biosensor for ATP Assay." Acta Chimica Sinica 71, no. 3 (2013): 367. http://dx.doi.org/10.6023/a12110962.

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39

Bing, Tao, Hongcheng Mei, Nan Zhang, Cui Qi, Xiangjun Liu, and Dihua Shangguan. "Exact tailoring of an ATP controlled streptavidin binding aptamer." RSC Advances 4, no. 29 (2014): 15111. http://dx.doi.org/10.1039/c4ra00714j.

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Xing, Xiaojing, Xueguo Liu, Ying Zhou, Dangdang Xu, Daiwen Pang, and Hongwu Tang. "Graphene oxide enhanced specificity at aptamer and its application to multiplexed enzymatic activity sensing." RSC Advances 6, no. 14 (2016): 11815–21. http://dx.doi.org/10.1039/c5ra25481g.

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41

Wang, Li, Li Fang, and Shufeng Liu. "Responsive hairpin DNA aptamer switch to program the strand displacement reaction for the enhanced electrochemical assay of ATP." Analyst 140, no. 17 (2015): 5877–80. http://dx.doi.org/10.1039/c5an00725a.

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42

Li, Yuqing, and Juewen Liu. "Aptamer-based strategies for recognizing adenine, adenosine, ATP and related compounds." Analyst 145, no. 21 (2020): 6753–68. http://dx.doi.org/10.1039/d0an00886a.

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Adenine, adenosine, ATP and related compounds are highly important in biology. A variety of DNA and RNA aptamers have been found to selectively bind them. This article reviews important aptamers for them and their representative applications.
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43

Sun, Ning, Qi Guo, Jingwei Shao, Bin Qiu, Zhenyu Lin, K. Y. Wong, and Guonan Chen. "A signal-on fluorescence biosensor for detection of adenosine triphosphate based on click chemistry." Anal. Methods 6, no. 10 (2014): 3370–74. http://dx.doi.org/10.1039/c4ay00220b.

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Zhang, Yuting, Gabriela Figueroa-Miranda, Changtong Wu, Dieter Willbold, Andreas Offenhäusser, and Dirk Mayer. "Electrochemical dual-aptamer biosensors based on nanostructured multielectrode arrays for the detection of neuronal biomarkers." Nanoscale 12, no. 31 (2020): 16501–13. http://dx.doi.org/10.1039/d0nr03421e.

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Liu, Yong, Xinxin Shao, Zhiyuan Shi, and Quanshun Li. "Inhibition of cancer cell proliferation by adenosine triphosphate-triggered codelivery system of p53 gene and doxorubicin." Cancer Plus 1, no. 2 (June 25, 2019): 3. http://dx.doi.org/10.18063/cp.v1i2.239.

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The codelivery of drugs and genes by stimuli-responsive nanocarriers is a promising strategy for achieving an effective cancer treatment. In this study, an adenosine triphosphate (ATP)-responsive nanosystem was constructed to codeliver doxorubicin (DOX) and p53 gene based on an ATP-triggered aptamer and polyethyleneimine (PEI). In this system, DOX interacts with the GC-rich motif of duplex formed by the aptamer and its cDNA sequence. Then, a ternary nanocomplex DOX-Duplex/PEI/p53 was constructed using cationic carrier PEI25K for facilitating the intracellular delivery and release of p53 gene and DOX. The DOX-Duplex/PEI/p53 nanocomplex was found to possess an efficient anticancer effect, which was attributed to the ability of the system to trigger cell apoptosis and meanwhile block the cell cycle at G2 phase. The favorable antiproliferative effect was found to be associated with the rapid DOX and p53 gene release in response to the intracellular ATP concentration and the synergistic effect of therapeutic drug and gene.
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Zhao, Mingming, Xiaoxi Song, Jiahui Lu, Siwen Liu, Xuan Sha, Qi Wang, Xu Cao, Kai Xu, and Jingjing Li. "DNA aptamer-based dual-responsive nanoplatform for targeted MRI and combination therapy for cancer." RSC Advances 12, no. 7 (2022): 3871–82. http://dx.doi.org/10.1039/d1ra08373b.

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A glutathione (GSH) and adenosine-5′-triphosphate (ATP) dual-sensitive nanoplatform was designed for controlled drug release and activatable MRI of tumors based on DNA aptamer and manganese dioxide (MnO2) nanosheets.
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Hou, Ting, Wei Li, Lianfang Zhang, and Feng Li. "A versatile and highly sensitive homogeneous electrochemical strategy based on the split aptamer binding-induced DNA three-way junction and exonuclease III-assisted target recycling." Analyst 140, no. 16 (2015): 5748–53. http://dx.doi.org/10.1039/c5an01176k.

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A versatile and highly sensitive homogeneous electrochemical biosensing platform has been developed for an ATP assay based on split aptamer binding-induced DNA three-way junction formation and Exo III-assisted target recycling.
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Wang, Jun, Yaxin Jiang, Cuisong Zhou, and Xiaohong Fang. "Aptamer-Based ATP Assay Using a Luminescent Light Switching Complex." Analytical Chemistry 77, no. 11 (June 2005): 3542–46. http://dx.doi.org/10.1021/ac050165w.

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Qiu, Huazhang, Zong’en Liu, Zhengjun Huang, Min Chen, Xiaohui Cai, Shaohuang Weng, and Xinhua Lin. "Aptamer based turn-off fluorescent ATP assay using DNA concatamers." Microchimica Acta 182, no. 15-16 (August 6, 2015): 2387–93. http://dx.doi.org/10.1007/s00604-015-1578-5.

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Liu, Jinhua, Jing Yu, Jianrong Chen, and Kaimin Shih. "Noncovalent assembly of carbon nanoparticles and aptamer for sensitive detection of ATP." RSC Adv. 4, no. 72 (2014): 38199–205. http://dx.doi.org/10.1039/c4ra05631k.

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Here base on competitive interaction of electrostatic repulsion and π–π stacking, noncovalent assembly of carbon nanoparticles (cCNPs) with aptamer that allows sensitive and selective detection of ATP is reported. The sensor exhibits minimal background fluorescence and rapid kinetics response depending on the spherical structure of cCNPs.
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