Relevance of G-quadruplex structures to pharmacogenetics

Cree, Simone L.; Kennedy, Martin A.

doi:10.3389/fphar.2014.00160

Cited by 29 publications

(18 citation statements)

References 83 publications

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“…This gene serves as an on and off switch that regulates cell differentiation and apoptosis. In another study, G4 ligands have been shown to forestall the incorporation of the HIV genome into the host genome by binding to and stabilizing G4s in the multi-domain HIV integrase enzyme ( Cree and Kennedy, 2014 ; Bala et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of G-Quadruplexes in African Swine Fever Virus Genome Reveals Potential Antiviral Targets by G-Quadruplex Stabilizers

et al. 2021

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African Swine Fever Virus (ASFV), a lethal hemorrhagic fever of the swine, poses a major threat to the world’s swine population and has so far resulted in devastating socio-economic consequences. The situation is further compounded by the lack of an approved vaccine or antiviral drug. Herein, we investigated a novel anti-ASFV approach by targeting G-Quadruplexes (G4s) in the viral genome. Bioinformatics analysis of putative G-quadruplex-forming sequences (PQSs) in the genome of ASFV BA71V strain revealed 317 PQSs on the forward strand and 322 PQSs on the reverse strand of the viral genome, translating to a density of 3.82 PQSs/kb covering 9.52% of the entire genome, which means that 85% of genes in the ASFV genome have at least 1 PQS on either strand. Biochemical characterization showed that 8 out of 13 conserved PQSs could form stable G4s in the presence of K+, and 4 of them could be stabilized by G4 ligands, N-Methyl Mesoporphyrin (NMM), and pyridostatin (PDS) in vitro. An enhanced green fluorescent protein (EGFP)-based reporter system revealed that the expression of two G4-containing genes, i.e., P1192R and D117L, could be significantly suppressed by NMM and PDS in 293T cells. In addition, a virus infection model showed that NMM could inhibit the replication of ASFV in Porcine Alveolar Macrophages (PAM) cells with an EC50 value of 1.16 μM. Altogether, the present study showed that functional PQSs existent in the promoters, CDS, 3′ and 5′ UTRs of the ASFV genome could be stabilized by G4 ligands, such as NMM and PDS, and could serve as potential targets for antivirals.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of G-Quadruplexes in African Swine Fever Virus Genome Reveals Potential Antiviral Targets by G-Quadruplex Stabilizers

et al. 2021

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“…Currently, there are over 200 crystal and NMRderived structures of quadruplexes present in the protein data bank. These G-quadruplex structures and their ligand complexes have been reviewed elsewhere in detail [8][9][10][11][12][13][14][15][16][17][18] . Positively charged alkali metal ions are essentially required for the stabilisation of the quadruplexes 19 .…”

Section: Review Articlementioning

confidence: 99%

Computational Methods to Study G-Quadruplex–Ligand Complexes

Haider

2018

J Indian Inst Sci

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“…It is well known that G-quartet structures play crucial roles in various cellular processes like in maintaining chromosomal ends, transcription, translation etc. [72] , along with their wide application in nanotechnology because of their self-assembly formation and stability [85] , [86] , [87] . The role of G-quadruplex structure in neurodegenerative diseases and non-coding transcriptome has also recently been reported [88] .…”

Section: Biological Applications Of Alternative Dna Structuresmentioning

confidence: 99%

A bouquet of DNA structures: Emerging diversity

Kaushik

Roy

et al. 2016

Biochemistry and Biophysics Reports

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Structural polymorphism of DNA has constantly been evolving from the time of illustration of the double helical model of DNA by Watson and Crick. A variety of non-canonical DNA structures have constantly been documented across the globe. DNA attracted worldwide attention as a carrier of genetic information. In addition to the classical Watson–Crick duplex, DNA can actually adopt diverse structures during its active participation in cellular processes like replication, transcription, recombination and repair. Structures like hairpin, cruciform, triplex, G-triplex, quadruplex, i-motif and other alternative non-canonical DNA structures have been studied at length and have also shown their in vivo occurrence. This review mainly focuses on non-canonical structures adopted by DNA oligonucleotides which have certain prerequisites for their formation in terms of sequence, its length, number and orientation of strands along with varied solution conditions. This conformational polymorphism of DNA might be the basis of different functional properties of a specific set of DNA sequences, further giving some insights for various extremely complicated biological phenomena. Many of these structures have already shown their linkages with diseases like cancer and genetic disorders, hence making them an extremely striking target for structure-specific drug designing and therapeutic applications.

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Relevance of G-quadruplex structures to pharmacogenetics

Cited by 29 publications

References 83 publications

Comprehensive Analysis of G-Quadruplexes in African Swine Fever Virus Genome Reveals Potential Antiviral Targets by G-Quadruplex Stabilizers

Comprehensive Analysis of G-Quadruplexes in African Swine Fever Virus Genome Reveals Potential Antiviral Targets by G-Quadruplex Stabilizers

Computational Methods to Study G-Quadruplex–Ligand Complexes

A bouquet of DNA structures: Emerging diversity

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