A short peptide that preferentially binds c-MYC G-quadruplex DNA

G-quadruplexes are nucleic-acids secondary structures that are highly abundant in the human genome. In this work,we identified a short-peptide that displays selectivity for the G-quadruplex formed in the promoter region of the oncogene c-MYC.

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Control of bacterial nitrate assimilation by stabilization of G-quadruplex DNA

Chemical Communications ◽

10.1039/c6cc06057a ◽

2016 ◽

Vol 52 (92) ◽

pp. 13511-13514 ◽

Cited By ~ 17

Author(s):

Zoë A. E. Waller ◽

Benjamin J. Pinchbeck ◽

Bhovina Seewoodharry Buguth ◽

Timothy G. Meadows ◽

David J. Richardson ◽

...

Keyword(s):

Promoter Region ◽

Paracoccus Denitrificans ◽

Nitrate Assimilation ◽

Quadruplex Dna ◽

G Quadruplex ◽

Specific Control

Ligand-specific control of nitrate assimilation inParacoccus denitrificansby stabilization of DNA G-quadruplex in the promoter region ofnas.

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Encapsulation and Ultrasound-Triggered Release of G-Quadruplex DNA in Multilayer Hydrogel Microcapsules

Polymers ◽

10.3390/polym10121342 ◽

2018 ◽

Vol 10 (12) ◽

pp. 1342 ◽

Cited By ~ 4

Author(s):

Aaron Alford ◽

Brenna Tucker ◽

Veronika Kozlovskaya ◽

Jun Chen ◽

Nirzari Gupta ◽

...

Keyword(s):

Nucleic Acids ◽

Defense Mechanisms ◽

The Body ◽

Stimuli Responsive ◽

Triggered Release ◽

Quadruplex Dna ◽

Nucleic Acid Therapeutics ◽

Wide Range ◽

G Quadruplex ◽

Hydrogel Capsules

Nucleic acid therapeutics have the potential to be the most effective disease treatment strategy due to their intrinsic precision and selectivity for coding highly specific biological processes. However, freely administered nucleic acids of any type are quickly destroyed or rendered inert by a host of defense mechanisms in the body. In this work, we address the challenge of using nucleic acids as drugs by preparing stimuli responsive poly(methacrylic acid)/poly(N-vinylpyrrolidone) (PMAA/PVPON)n multilayer hydrogel capsules loaded with ~7 kDa G-quadruplex DNA. The capsules are shown to release their DNA cargo on demand in response to both enzymatic and ultrasound (US)-triggered degradation. The unique structure adopted by the G-quadruplex is essential to its biological function and we show that the controlled release from the microcapsules preserves the basket conformation of the oligonucleotide used in our studies. We also show that the (PMAA/PVPON) multilayer hydrogel capsules can encapsulate and release ~450 kDa double stranded DNA. The encapsulation and release approaches for both oligonucleotides in multilayer hydrogel microcapsules developed here can be applied to create methodologies for new therapeutic strategies involving the controlled delivery of sensitive biomolecules. Our study provides a promising methodology for the design of effective carriers for DNA vaccines and medicines for a wide range of immunotherapies, cancer therapy and/or tissue regeneration therapies in the future.

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Pif1 is essential for efficient replisome progression through lagging strand G-quadruplex DNA secondary structures

Nucleic Acids Research ◽

10.1093/nar/gky1065 ◽

2018 ◽

Vol 46 (22) ◽

pp. 11847-11857 ◽

Cited By ~ 23

Author(s):

Danielle Dahan ◽

Ioannis Tsirkas ◽

Daniel Dovrat ◽

Melanie A Sparks ◽

Saurabh P Singh ◽

...

Keyword(s):

Secondary Structures ◽

Quadruplex Dna ◽

G Quadruplex ◽

Dna Secondary Structures ◽

Lagging Strand

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Light-Induced Formation of G-Quadruplex DNA Secondary Structures

ChemBioChem ◽

10.1002/cbic.200500198 ◽

2005 ◽

Vol 6 (11) ◽

pp. 1966-1970 ◽

Cited By ~ 57

Author(s):

Günter Mayer ◽

Lenz Kröck ◽

Vera Mikat ◽

Marianne Engeser ◽

Alexander Heckel

Keyword(s):

Secondary Structures ◽

Quadruplex Dna ◽

G Quadruplex ◽

Dna Secondary Structures

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Perspectives for Applying G-Quadruplex Structures in Neurobiology and Neuropharmacology

International Journal of Molecular Sciences ◽

10.3390/ijms20122884 ◽

2019 ◽

Vol 20 (12) ◽

pp. 2884 ◽

Cited By ~ 13

Author(s):

Sefan Asamitsu ◽

Masayuki Takeuchi ◽

Susumu Ikenoshita ◽

Yoshiki Imai ◽

Hirohito Kashiwagi ◽

...

Keyword(s):

Neurological Disorders ◽

Neurological Diseases ◽

Secondary Structures ◽

Neuronal Function ◽

Double Stranded Rna ◽

Quadruplex Dna ◽

Functional Roles ◽

G Quadruplex ◽

Dna Secondary Structures

The most common form of DNA is a right-handed helix or the B-form DNA. DNA can also adopt a variety of alternative conformations, non-B-form DNA secondary structures, including the DNA G-quadruplex (DNA-G4). Furthermore, besides stem-loops that yield A-form double-stranded RNA, non-canonical RNA G-quadruplex (RNA-G4) secondary structures are also observed. Recent bioinformatics analysis of the whole-genome and transcriptome obtained using G-quadruplex–specific antibodies and ligands, revealed genomic positions of G-quadruplexes. In addition, accumulating evidence pointed to the existence of these structures under physiologically- and pathologically-relevant conditions, with functional roles in vivo. In this review, we focused on DNA-G4 and RNA-G4, which may have important roles in neuronal function, and reveal mechanisms underlying neurological disorders related to synaptic dysfunction. In addition, we mention the potential of G-quadruplexes as therapeutic targets for neurological diseases.

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Effect of Ionic Strength on Porphyrin Drugs Interaction with Quadruplex DNA Formed by the Promoter Region of C-myc and Bcl2 Oncogenes

Journal of Nucleic Acids ◽

10.4061/2010/146418 ◽

2010 ◽

Vol 2010 ◽

pp. 1-9 ◽

Cited By ~ 18

Author(s):

Narayana Nagesh ◽

Varun K. Sharma ◽

A. Ganesh Kumar ◽

Edwin A. Lewis

Keyword(s):

Ionic Strength ◽

Fluorescence Spectroscopy ◽

Drug Interactions ◽

Promoter Region ◽

Promoter Regions ◽

Quadruplex Dna ◽

Quadruplex Structure ◽

G Quadruplex ◽

Drugs Interaction ◽

Dna Complex

C-myc and Bcl2 are well characterized oncogenes that are capable of forming G-quadruplex structures. Promoter regions of C-myc and Bcl2 forming G-quadruplex structures are chemically synthesized and G-quadruplex structure is formed in presence of 100 mM potassium ion. Three different porphyrin drugs, namely TMPyP2, TMPyP3, and TMPyP4 are allowed to interact with quadruplex DNA complex and the site and nature of interaction are studied. Drug interactions with quadruplex DNA were carried out in different potassium ionic strengths using fluorescence spectroscopy. It is found that fluorescence hypochromicity decreases with an increase in ionic strength in the case of TMPyP4, TMPyP3, and TMPyP2. Fluorescence titration studies and Job plots indicate that four molecules of TMPyP4, two molecules of TMPyP3 and TMPyP2 are interacting with one molecule of quadruplex DNA.

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Covalently Functionalized DNA Duplexes and Quadruplexes as Hybrid Catalysts in an Enantioselective Friedel–Crafts Reaction

Molecules ◽

10.3390/molecules25143121 ◽

2020 ◽

Vol 25 (14) ◽

pp. 3121

Author(s):

Surjendu Dey ◽

Andres Jäschke

Keyword(s):

Secondary Structures ◽

Catalytic Performance ◽

Dna Duplexes ◽

Quadruplex Dna ◽

Hybrid Catalysts ◽

Modified Dna ◽

G Quadruplex ◽

Dna Secondary Structures ◽

Dna Strand

The precise site-specific positioning of metal–ligand complexes on various DNA structures through covalent linkages has gained importance in the development of hybrid catalysts for aqueous-phase homogeneous catalysis. Covalently modified double-stranded and G-quadruplex DNA-based hybrid catalysts have been investigated separately. To understand the role of different DNA secondary structures in enantioselective Friedel–Crafts alkylation, a well-known G-quadruplex-forming sequence was covalently modified at different positions. The catalytic performance of this modified DNA strand was studied in the presence and absence of a complementary DNA sequence, resulting in the formation of two different secondary structures, namely duplex and G-quadruplex. Indeed, the secondary structures had a tremendous effect on both the yield and stereoselectivity of the catalyzed reaction. In addition, the position of the modification, the topology of the DNA, the nature of the ligand, and the length of the linker between ligand and DNA were found to modulate the catalytic performance of the hybrid catalysts. Using the optimal linker length, the quadruplexes formed the (−)-enantiomer with up to 65% ee, while the duplex yielded the (+)-enantiomer with up to 62% ee. This study unveils a new and simple way to control the stereochemical outcome of a Friedel–Crafts reaction.

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Interaction of TMPyP4, TMPyP3, and TMPyP2 with Intramolecular G-Quadruplex Formed by Promoter Region of Bcl2 and KRAS NHPPE

ISRN Biophysics ◽

10.5402/2012/786596 ◽

2012 ◽

Vol 2012 ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Narayana Nagesh ◽

Arumugam Ganesh Kumar

Keyword(s):

Promoter Region ◽

Dna Interaction ◽

Predominant Role ◽

Promoter Regions ◽

Ligand Interaction ◽

Quadruplex Dna ◽

Molecular Binding ◽

Quadruplex Structure ◽

G Quadruplex ◽

Structure Environment

Oncogenes are rich in guanine and capable of forming quadruplex structure. Promoter regions oncogenes such as Bcl2 and KRAS NHPPE are rich in guanine content and they can form quadruplex structures. Alterations in the mode and nature of molecular binding to DNA, certainly has effect on the posttranscriptional activities. Recent experiments indicate that structure of quadruplex complex and ligand has predominant role on ligand-quadruplex DNA interaction. In order to understand the nature of each ligand interaction with quadruplex DNA, Bcl2, KRAS NHPPE quadruplex DNA interaction with three porphyrin was studied using spectroscopy, microcalorimetry and mass spectrometry. Our studies, indicate that mode of ligand interaction varies with structure, environment and concentration of ligand. Fluorescence quenching experiments show that TMPyP4 interaction is ligand concentration dependent. Job plots and ITC experiments demonstrate that four molecules of TMPyP4 and two molecules of TMPyP3, TMPyP2 interact with each quadruplex complex. Through ITC titrations, ligand binding constant are higher for TMPyP4 (≈107 M−1) compared to TMPyP3, TMPyP2 (≈105 M−1). ESI-MS experiments confirm the stoichiometry of TMPyP4 : 39Bcl2 is 4 : 1 at saturation and it is 2 : 1 in case of KRAS NHPPE quadruplex.

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