G‐Rich Sequence‐Specific Recognition and Scission of Human Genome by PNA/DNA Hybrid G‐Quadruplex Formation

Ishizuka, Takumi; Yang, Jie; Komiyama, Makoto; Xu, Yan

doi:10.1002/ange.201201176

Cited by 7 publications

(3 citation statements)

References 44 publications

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“…PNAs have been initially developed for hybridization to duplex DNA for a higher thermodynamic stability of PNA–DNA duplexes compared to DNA–DNA duplexes. Various PNA oligomers have been reported to recognize noncanonical DNA/RNA G-quadruplexes (G4) by forming heteroduplexes or heteroquadruplexes. − Phan et al reported that guanine-linked PNA can stabilize a particular G4 by dual recognition . Panyutin and co-workers illustrated short PNA oligomers can induce BCL2 G4 formation using C-strand-invading short PNAs .…”

Section: Introductionmentioning

confidence: 99%

Thiazole Containing PNA Mimic Regulates c-MYC Gene Expression through DNA G-Quadruplex

et al. 2022

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Peptide nucleic acids (PNAs), besides hybridizing to complementary DNA and RNAs, bind and stabilize DNA secondary structures. Herein, we illustrate the design and synthesis of PNA-like scaffolds by incorporating five-membered thiazole rings as modified bases instead of nucleobases and their subsequent effects on gene regulation by biophysical and in vitro assays. A thiazole-modified PNA trimer selectively recognizes c-MYC G-quadruplex (G4) DNA over other G4s and duplex DNA.It displays a high stabilization potential for the c-MYC G4 DNA and shows remarkable fluorescence enhancement with the c-MYC G4. It is flexible enough to bind at 5′ and 3′ ends as well as in the groove region of c-MYC G4. Furthermore, the PNA trimer easily permeates the cellular membrane and suppresses c-MYC mRNA expression in HeLa cells by targeting the promoter G4. This study illuminates modified PNAs as flexible molecular tools for selective targeting of noncanonical nucleic acids and modulating gene function.

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Section: Introductionmentioning

confidence: 99%

Thiazole Containing PNA Mimic Regulates c-MYC Gene Expression through DNA G-Quadruplex

et al. 2022

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“…Interestingly, previous reports have shown that PNA is capable of sequence-specific binding to DNA, obeying the Watson-Crick pattern, to form a double helix [12, 13]. PNA may also recognize particular DNA sequences to generate other complex yet specific helical structures such as triplex or quadruplex [14–16]. For example, a unique “P-form” triple helix conformation comprising two polypyrimidine PNAs and one polypurine DNA can be achieved via combination of Watson–Crick and Hoogsteen base interactions [14].…”

Section: Introductionmentioning

confidence: 99%

Hybrid polymeric hydrogels via peptide nucleic acid (PNA)/DNA complexation

Chu

Feng

Yang

et al. 2015

Journal of Controlled Release

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This work presents a new concept in hybrid hydrogel design. Synthetic water-soluble N-(2-hydroxypropyl)methacrylamide (HPMA) polymers grafted with multiple peptide nucleic acids (PNA) are crosslinked upon addition of the linker DNA. The self-assembly is mediated by the PNA–DNA complexation, which results in the formation of hydrophilic polymer networks. We show that the hydrogels can be produced through two different types of complexations. Type I hydrogel is formed via the PNA/DNA double-helix hybridization. Type II hydrogel utilizes a unique “P-form” oligonucleotide triple-helix that comprises two PNA sequences and one DNA. Microrheology studies confirm the respective gelation processes and disclose a higher critical gelation concentration for the type I gel when compared to the type II design. Scanning electron microscopy reveals the interconnected microporous structure of both types of hydrogels. Type I double-helix hydrogel exhibits larger pore sizes than type II triple-helix gel. The latter apparently contains denser structure and displays greater elasticity as well. The designed hybrid hydrogels have potential as novel biomaterials for pharmaceutical and biomedical applications.

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“…The resulting quadruplexes were found to consist of two PNA and two DNA molecules (i.e., the stoichiometry of DNA to PNA was 1:1). Later the double invasion was used for sequence-specific scission of a double-stranded plasmid and genomic DNA [14]. However, the strand arrangements and stoichiometry of the DNA-PNA quadruplex complexes were not determined in these studies.…”

mentioning

confidence: 99%

G-Quadruplex Formation Between G-Rich PNA and Homologous Sequences in Oligonucleotides and Supercoiled Plasmid DNA

Gaynutdinov

Englund

Appella

et al. 2015

Nucleic Acid Therapeutics

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Guanine (G)-rich DNA sequences can adopt four-stranded quadruplex conformations that may play a role in the regulation of genetic processes. To explore the possibility of targeted molecular recognition of DNA sequences with short G-rich peptide nucleic acids (PNA) and to assess the strand arrangement in such complexes, we used PNA and DNA with the Oxytricha nova telomeric sequence d(G 4 T 4 G 4 ) as a model. PNA probes were complexed with DNA targets in the following forms: single-stranded oligonucleotides, a loop of DNA in a hairpin conformation, and as supercoiled plasmid with the (G 4 T 4 G 4 )/(C 4 A 4 C 4 ) insert. Gel-shift mobility assays demonstrated formation of stable hybrid complexes between the homologous G 4 T 4 G 4 PNA and DNA with multiple modes of binding. Chemical and enzymatic probing revealed sequence-specific and G-quadruplex dependent binding of G 4 T 4 G 4 PNA to dsDNA. Spectroscopic and electrophoretic analysis of the complex formed between PNA and the synthetic DNA hairpin containing the G 4 T 4 G 4 loop showed that the stoichiometry of a prevailing complex is three PNA strands per one DNA strand. We speculate how this new PNA-DNA complex architecture can help to design more selective, quadruplex-specific PNA probes.

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G‐Rich Sequence‐Specific Recognition and Scission of Human Genome by PNA/DNA Hybrid G‐Quadruplex Formation

Cited by 7 publications

References 44 publications

Thiazole Containing PNA Mimic Regulates c-MYC Gene Expression through DNA G-Quadruplex

Thiazole Containing PNA Mimic Regulates c-MYC Gene Expression through DNA G-Quadruplex

Hybrid polymeric hydrogels via peptide nucleic acid (PNA)/DNA complexation

G-Quadruplex Formation Between G-Rich PNA and Homologous Sequences in Oligonucleotides and Supercoiled Plasmid DNA

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