Alkylation of phosphorothioated thrombin binding aptamers improves the selectivity of inhibition of tumor cell proliferation upon anticoagulation

Yang, Xiantao; Zhu, Yuejie; Wang, Chao; Zhu, Ge; Zhang, Lihe; Yang, Zhenjun

doi:10.1016/j.bbagen.2017.04.002

Cited by 14 publications

(8 citation statements)

References 24 publications

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“… 12 Thus, the appropriate chemical modification was requisite to improve their chemical and biological properties, which is known as Post-SELEX. Many types of chemical modifications have been developed, including nucleobase, 13 sugar ring 14 and backbone 15 , 16 modification, aiming at improving nuclease resistance, pharmacokinetic properties and activity.…”

Section: Introductionmentioning

confidence: 99%

The Bioactivity of D-/L-Isonucleoside- and 2′-Deoxyinosine-Incorporated Aptamer AS1411s Including DNA Replication/MicroRNA Expression

Fan

Sun

et al. 2017

Molecular Therapy - Nucleic Acids

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In this study, chemical modification of 2′-deoxyinosine (2′-dI) and D-/L-isothymidine (D-/L-isoT) was performed on AS1411. They could promote the nucleotide-protein interaction by changing the local conformation. Twenty modified sequences were obtained, FCL-I and FCL-II showed the most noticeable activity improvement. They stabilized the G-quadruplex, remained highly resistant to serum degradation and specificity for nucleolin, further inhibited tumor cell growth, exhibited a stronger ability to influence the different phases of the tumor cell cycle, induced S-phase arrest, promoted the inhibition of DNA replication, and suppressed the unwound function of a large T antigen as powerful as AS1411. The microarray analysis and TaqMan PCR results showed that FCL-II can upregulate the expression of four breast-cancer-related, lowly expressed miRNAs and downregulate the expression of three breast-cancer-related, highly expressed miRNAs (>2.5-fold). FCL-II resulted in enhanced treatment effects greater than AS1411 in animal experiments (p < 0.01). The computational results further proved that FCL-II exhibits more structural advantages than AS1411 for binding to the target protein nucleolin, indicating its great potential in antitumor therapy.

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Section: Introductionmentioning

confidence: 99%

The Bioactivity of D-/L-Isonucleoside- and 2′-Deoxyinosine-Incorporated Aptamer AS1411s Including DNA Replication/MicroRNA Expression

Fan

Sun

et al. 2017

Molecular Therapy - Nucleic Acids

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“…Another possibility is the thrombin-binding aptamer (TBA) analogue, TBA535. TBA presents both anticoagulant [ 49 ] and anti-proliferative properties [ 50 , 51 , 52 , 53 ], but through inversion of polarity sites TBA535 was able to fold in a unique G4 structure and endowed with a better anti-proliferative activity in Calu-6 lung cancer cells but no anticoagulant activity [ 54 ]. Additionally, through wound healing assay, the authors shown that both TBA and TBA535 exhibit anti-motility properties [ 54 ].…”

Section: G-quadruplex Structures As Drug Delivery Systemsmentioning

confidence: 99%

G-Quadruplex-Based Drug Delivery Systems for Cancer Therapy

2021

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G-quadruplexes (G4s) are a class of nucleic acids (DNA and RNA) with single-stranded G-rich sequences. Owing to the selectivity of some G4s, they are emerging as targeting agents to overtake side effects of several potential anticancer drugs, and delivery systems of small molecules to malignant cells, through their high affinity or complementarity to specific targets. Moreover, different systems are being used to improve their potential, such as gold nano-particles or liposomes. Thus, the present review provides relevant data about the different studies with G4s as drug delivery systems and the challenges that must be overcome in the future research.

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“…The possibilities for the modification at the level of the phosphate unit are more limited than in the case of the sugar and nucleobases moieties and most efforts have focused on the α-phosphate, particularly α-phosphorothioates [ 242 , 279 , 292 , 293 , 294 ]. In this context, Yang et al have explored the alkylation of phosphorothioated thrombine-binding aptamers (TBA) with aim of improving the antitumor properties of the ligands by reducing the thrombin binding affinity [ 295 ]. Alkylation of the phosphorothiate moieties was achieved by a simple substitution reaction with four different brominated substrates ( 10 to 13 in Figure 9 ).…”

Section: Recent Chemical Modifications Of Aptamersmentioning

confidence: 99%

Nucleic Acid Aptamers: Emerging Applications in Medical Imaging, Nanotechnology, Neurosciences, and Drug Delivery

Röthlisberger

Gasse

Hollenstein

2017

IJMS

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Recent progresses in organic chemistry and molecular biology have allowed the emergence of numerous new applications of nucleic acids that markedly deviate from their natural functions. Particularly, DNA and RNA molecules—coined aptamers—can be brought to bind to specific targets with high affinity and selectivity. While aptamers are mainly applied as biosensors, diagnostic agents, tools in proteomics and biotechnology, and as targeted therapeutics, these chemical antibodies slowly begin to be used in other fields. Herein, we review recent progress on the use of aptamers in the construction of smart DNA origami objects and MRI and PET imaging agents. We also describe advances in the use of aptamers in the field of neurosciences (with a particular emphasis on the treatment of neurodegenerative diseases) and as drug delivery systems. Lastly, the use of chemical modifications, modified nucleoside triphosphate particularly, to enhance the binding and stability of aptamers is highlighted.

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Alkylation of phosphorothioated thrombin binding aptamers improves the selectivity of inhibition of tumor cell proliferation upon anticoagulation

Cited by 14 publications

References 24 publications

The Bioactivity of D-/L-Isonucleoside- and 2′-Deoxyinosine-Incorporated Aptamer AS1411s Including DNA Replication/MicroRNA Expression

The Bioactivity of D-/L-Isonucleoside- and 2′-Deoxyinosine-Incorporated Aptamer AS1411s Including DNA Replication/MicroRNA Expression

G-Quadruplex-Based Drug Delivery Systems for Cancer Therapy

Nucleic Acid Aptamers: Emerging Applications in Medical Imaging, Nanotechnology, Neurosciences, and Drug Delivery

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