Potential uses of G-quadruplex-forming aptamers

Víglaský, Viktor; Hianik, Tibor

doi:10.4149/gpb_2013019

Cited by 40 publications

(35 citation statements)

References 158 publications

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“…We utilized the G4 Predictor tool, G4IPDB 26 ( http://bsbe.iiti.ac.in/bsbe/ipdb/pattern2.php ), and the prevalent QGRS Mapper 27 tool ( http://bioinformatics.ramapo.edu/QGRS/index.php ) to predict the number and distribution of quadruplex-forming G-rich sequences (QGRS) with high accuracy. 27 , 28 Both HupB-4T and HupB-13T aptamers evinced high G scores (range 21–34) that was comparable or even exceeded the QGRS Mapper predicted G scores of established G-quadruplex-forming aptamers such as Thrombin 29 and anti-VEGF 30 ( Table S4 ). Analysis of these aptamers on non-denaturing PAGE provided experimental support, as both HupB-4T and HupB-13T aptamers migrated as multiple bands of higher molecular weight, unlike the control oligo 1 ( Figure 4 A), confirming formation of intra- (monomer) and inter-molecular structures (di- or tetramers) typically present in G-quadruplex-forming aptamers.…”

Section: Resultsmentioning

confidence: 93%

G-Quadruplex-Forming DNA Aptamers Inhibit the DNA-Binding Function of HupB and Mycobacterium tuberculosis Entry into Host Cells

Kalra

Mishra

Kaur

et al. 2018

Molecular Therapy - Nucleic Acids

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The entry and survival of Mycobacterium tuberculosis (Mtb) within host cells is orchestrated partly by an essential histone-like protein HupB (Rv2986c). Despite being an essential drug target, the lack of structural information has impeded the development of inhibitors targeting the indispensable and multifunctional C-terminal domain (CTD) of HupB. To bypass the requirement for structural information in the classical drug discovery route, we generated a panel of DNA aptamers against HupB protein through systemic evolution of ligands by exponential (SELEX) enrichment. Two G-quadruplex-forming high-affinity aptamers (HupB-4T and HupB-13T) were identified, each of which bound two distinct sites on full-length HupB, with an estimated KD of ∼1.72 μM and ∼0.17 μM, respectively, for the high-affinity sites. While HupB-4T robustly inhibited DNA-binding activity of HupB in vitro, both the aptamers recognized surface-located HupB and significantly blocked Mtb entry into THP-1 monocytic cells (p < 0.0001). In summary, DNA aptamers generated in this study block DNA-binding activity of HupB, inhibit virulent Mtb infection in host cells, and demonstrate aptamers to be inhibitors of HupB functions. This study also illustrates the utility of SELEX in developing inhibitors against essential targets for whom structural information is not available.

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Section: Resultsmentioning

confidence: 93%

G-Quadruplex-Forming DNA Aptamers Inhibit the DNA-Binding Function of HupB and Mycobacterium tuberculosis Entry into Host Cells

Kalra

Mishra

Kaur

et al. 2018

Molecular Therapy - Nucleic Acids

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“…It has been reported that the combination of NMM and G-quadruplex can detect metal ions ( Liu et al, 2011 ). G-quadruplex is widely used in biosensors to detect organic molecules ( Viglasky and Hianik, 2013 ), nucleic acids ( Tang et al, 2012 ), biological enzymes ( Wang et al, 2015b )and metal ions ( Guo et al, 2012 ). In recent years, G-quadruplex based biosensors have been intensively studied.…”

Section: Introductionmentioning

confidence: 99%

G-quadruplex based biosensor: A potential tool for SARS-CoV-2 detection

Juhas

Zhang

2020

Biosensors and Bioelectronics

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G-quadruplex is a non-canonical nucleic acid structure formed by the folding of guanine rich DNA or RNA. The conformation and function of G-quadruplex are determined by a number of factors, including the number and polarity of nucleotide strands, the type of cations and the binding targets. Recent studies led to the discovery of additional advantageous attributes of G-quadruplex with the potential to be used in novel biosensors, such as improved ligand binding and unique folding properties. G-quadruplex based biosensor can detect various substances, such as metal ions, organic macromolecules, proteins and nucleic acids with improved affinity and specificity compared to standard biosensors. The recently developed G-quadruplex based biosensors include electrochemical and optical biosensors. A novel G-quadruplex based biosensors also show better performance and broader applications in the detection of a wide spectrum of pathogens, including SARS-CoV-2, the causative agent of COVID-19 disease. This review highlights the latest developments in the field of G-quadruplex based biosensors, with particular focus on the G-quadruplex sequences and recent applications and the potential of G-quadruplex based biosensors in SARS-CoV-2 detection.

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“…S4. We evaluated the interaction of the peptide-TBA conjugates with a range of agreement with those reported in literature for aptasensors [60,61], in the order of sub nanomolar discarding the SPR biosensors that enhance their sensitivity by means of amplification procedures or by exploiting the properties of nanoparticles [62].…”

Section: Spr Analysis Of the Tba-peptide Conjugates With α-Thrombinmentioning

confidence: 99%

Aptamer-peptide conjugates as a new strategy to modulate human α-thrombin binding affinity

Aviñó

Jorge

Huertas

et al. 2019

Biochimica et Biophysica Acta (BBA) - General Subjects

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Aptamers are single-stranded RNA or DNA molecules that specifically recognize their targets and have proven valuable for functionalizing sensitive biosensors. α-thrombin is a trypsin like serine proteinase which plays a crucial role in haemostasis and thrombosis. An abnormal activity or overexpression of this protein is associated with a variety of diseases. A great deal of attention was devoted to the construction of high-throughput biosensors for accurately detect thrombin for the early diagnosis and treatment of related diseases. Herein, we propose a new approach to modulate the interaction between α-thrombin and the aptamer TBA 15. To this end, TBA 15 was chemically conjugated to two peptide sequences (TBA-G 3 FIE-Ac and TBA-G 3 EIF-Ac) corresponding to a short fragment of the acidic region of the human factor V, which is known to interact directly with exosite I. Surface Plasmon Resonance (SPR) results showed enhanced analytical performances of thrombin with TBA-G 3 EIF-Ac than with TBA wild-type, reaching a limit of detection as low as 44.9 pM. Electrophoresis mobility shift assay (EMSA) corroborated the SPR results. Molecular dynamics (MD) simulations support experimental evidences and provided further insight into thrombin/TBA-peptide interaction. Our findings demonstrate that the combination of TBA 15 with key interacting peptides offers good opportunities to produce sensitive devices for thrombin detection and potential candidates to block thrombin activity.

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Potential uses of G-quadruplex-forming aptamers

Cited by 40 publications

References 158 publications

G-Quadruplex-Forming DNA Aptamers Inhibit the DNA-Binding Function of HupB and Mycobacterium tuberculosis Entry into Host Cells

G-Quadruplex-Forming DNA Aptamers Inhibit the DNA-Binding Function of HupB and Mycobacterium tuberculosis Entry into Host Cells

G-quadruplex based biosensor: A potential tool for SARS-CoV-2 detection

Aptamer-peptide conjugates as a new strategy to modulate human α-thrombin binding affinity

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