scholarly journals Insight into the Complexity of the i-Motif and G-Quadruplex DNA Structures Formed in the KRAS Promoter and Subsequent Drug-Induced Gene Repression

2017 ◽  
Vol 139 (25) ◽  
pp. 8522-8536 ◽  
Author(s):  
Christine E. Kaiser ◽  
Natalie A. Van Ert ◽  
Prashansa Agrawal ◽  
Reena Chawla ◽  
Danzhou Yang ◽  
...  
Keyword(s):  
Gene Repression ◽  
Drug Induced ◽  
Quadruplex Dna ◽  
Dna Structures ◽  
G Quadruplex ◽  
Insight Into

scholarly journals DNA G-quadruplexes for native mass spectrometry in potassium: a database of validated structures in electrospray-compatible conditions

2021 ◽  
Author(s):  
Anirban Ghosh ◽  
Eric Largy ◽  
Valérie Gabelica
Keyword(s):  
Mass Spectrometry ◽  
Drug Targets ◽  
Native Mass Spectrometry ◽  
Drug Binding ◽  
Quadruplex Dna ◽  
Dna Structures ◽  
Nmr Structures ◽  
G Quadruplex ◽  
Screening Assays

Abstract G-quadruplex DNA structures have become attractive drug targets, and native mass spectrometry can provide detailed characterization of drug binding stoichiometry and affinity, potentially at high throughput. However, the G-quadruplex DNA polymorphism poses problems for interpreting ligand screening assays. In order to establish standardized MS-based screening assays, we studied 28 sequences with documented NMR structures in (usually ∼100 mM) potassium, and report here their circular dichroism (CD), melting temperature (Tm), NMR spectra and electrospray mass spectra in 1 mM KCl/100 mM trimethylammonium acetate. Based on these results, we make a short-list of sequences that adopt the same structure in the MS assay as reported by NMR, and provide recommendations on using them for MS-based assays. We also built an R-based open-source application to build and consult a database, wherein further sequences can be incorporated in the future. The application handles automatically most of the data processing, and allows generating custom figures and reports. The database is included in the g4dbr package (https://github.com/EricLarG4/g4dbr) and can be explored online (https://ericlarg4.github.io/G4_database.html).

G-quadruplex DNA structures and their relevance in radioprotection

2021 ◽  
Vol 1865 (5) ◽  
pp. 129857
Author(s):  
Nitu Kumari ◽  
Sathees C. Raghavan
Keyword(s):  
Quadruplex Dna ◽  
Dna Structures ◽  
G Quadruplex

scholarly journals Subtle structural alterations in G-quadruplex DNA regulate site specificity of fluorescence light-up probes

2020 ◽  
Vol 48 (3) ◽  
pp. 1108-1119 ◽  
Author(s):  
Rajendra Kumar ◽  
Karam Chand ◽  
Sudipta Bhowmik ◽  
Rabindra Nath Das ◽  
Snehasish Bhattacharjee ◽  
...  
Keyword(s):  
Rational Design ◽  
Dna Structure ◽  
Biological Processes ◽  
Chemical Research ◽  
Quadruplex Dna ◽  
Dna Structures ◽  
Future Studies ◽  
G4 Dna ◽  
G Quadruplex ◽  
Fluorescence Light

Abstract G-quadruplex (G4) DNA structures are linked to key biological processes and human diseases. Small molecules that target specific G4 DNA structures and signal their presence would therefore be of great value as chemical research tools with potential to further advance towards diagnostic and therapeutic developments. However, the development of these types of specific compounds remain as a great challenge. In here, we have developed a compound with ability to specifically signal a certain c-MYC G4 DNA structure through a fluorescence light-up mechanism. Despite the compound's two binding sites on the G4 DNA structure, only one of them result in the fluorescence light-up effect. This G-tetrad selectivity proved to originate from a difference in flexibility that affected the binding affinity and tilt the compound out of the planar conformation required for the fluorescence light-up mechanism. The intertwined relation between the presented factors is likely the reason for the lack of examples using rational design to develop compounds with turn-on emission that specifically target certain G4 DNA structures. However, this study shows that it is indeed possible to develop such compounds and present insights into the molecular details of specific G4 DNA recognition and signaling to advance future studies of G4 biology.

scholarly journals Specific Photocleavage Activity of N ‐Methylmesoporphyrin IX on G‐Quadruplex DNA Structures

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Ruby A Escobedo ◽  
Kimberly J Long ◽  
Dominic N McBrayer ◽  
Michelle Schoonover ◽  
Sean M Kerwin
Keyword(s):  
Quadruplex Dna ◽  
Dna Structures ◽  
G Quadruplex

scholarly journals Dynamics Studies of DNA with Non-canonical Structure Using NMR Spectroscopy

2020 ◽  
Vol 21 (8) ◽  
pp. 2673 ◽  
Author(s):  
Kwang-Im Oh ◽  
Jinwoo Kim ◽  
Chin-Ju Park ◽  
Joon-Hwa Lee
Keyword(s):  
Nmr Spectroscopy ◽  
Biological Function ◽  
Conformational Exchange ◽  
Biological Processes ◽  
Dynamic Characterization ◽  
Dynamic Features ◽  
Dna Structures ◽  
Left Handed ◽  
G Quadruplex ◽  
Insight Into

The non-canonical structures of nucleic acids are essential for their diverse functions during various biological processes. These non-canonical structures can undergo conformational exchange among multiple structural states. Data on their dynamics can illustrate conformational transitions that play important roles in folding, stability, and biological function. Here, we discuss several examples of the non-canonical structures of DNA focusing on their dynamic characterization by NMR spectroscopy: (1) G-quadruplex structures and their complexes with target proteins; (2) i-motif structures and their complexes with proteins; (3) triplex structures; (4) left-handed Z-DNAs and their complexes with various Z-DNA binding proteins. This review provides insight into how the dynamic features of non-canonical DNA structures contribute to essential biological processes.

scholarly journals N-methyl mesoporphyrin IX as a highly selective light-up probe for G-quadruplex DNA

2019 ◽  
Vol 23 (11n12) ◽  
pp. 1195-1215 ◽  
Author(s):  
Ariana Yett ◽  
Linda Yingqi Lin ◽  
Dana Beseiso ◽  
Joanne Miao ◽  
Liliya A. Yatsunyk
Keyword(s):  
Optical Properties ◽  
Small Molecules ◽  
Genomic Stability ◽  
Water Soluble ◽  
Biological Processes ◽  
Binding Properties ◽  
Quadruplex Dna ◽  
Dna Structures ◽  
G Quadruplex ◽  
High Fluorescence

[Formula: see text]-methyl mesoporphyrin IX (NMM) is a water-soluble, non-symmetric porphyrin with excellent optical properties and unparalleled selectivity for G-quadruplex (GQ) DNA. G-quadruplexes are non-canonical DNA structures formed by guanine-rich sequences. They are implicated in genomic stability, longevity, and cancer. The ability of NMM to selectively recognize GQ structures makes it a valuable scaffold for designing novel GQ binders. In this review, we survey the literature describing the GQ-binding properties of NMM as well as its wide utility in chemistry and biology. We start with the discovery of the GQ-binding properties of NMM and the development of NMM-binding aptamers. We then discuss the optical properties of NMM, focusing on the light-switch effect — high fluorescence of NMM induced upon its binding to GQ DNA. Additionally, we examine the affinity and selectivity of NMM for GQs, as well as its ability to stabilize GQ structures and favor parallel GQ conformations. Furthermore, a portion of the review is dedicated to the applications of NMM-GQ complexes as biosensors for heavy metals, small molecules ([Formula: see text] ATP and pesticides), DNA, and proteins. Finally and importantly, we discuss the utility of NMM as a probe to investigate the roles of GQs in biological processes.

scholarly journals Mgs1 protein supports genome stability via recognition of G‐quadruplex DNA structures

2020 ◽  
Vol 34 (9) ◽  
pp. 12646-12662 ◽  
Author(s):  
Theresa Zacheja ◽  
Agnes Toth ◽  
Gabor M. Harami ◽  
Qianlu Yang ◽  
Eike Schwindt ◽  
...  
Keyword(s):  
Genome Stability ◽  
Quadruplex Dna ◽  
Dna Structures ◽  
G Quadruplex

scholarly journals Macrocyclization of bis-indole quinolines for selective stabilization of G-quadruplex DNA structures

2020 ◽  
Vol 11 (38) ◽  
pp. 10529-10537 ◽  
Author(s):  
Rabindra Nath Das ◽  
Måns Andréasson ◽  
Rajendra Kumar ◽  
Erik Chorell
Keyword(s):  
Quadruplex Dna ◽  
Dna Structures ◽  
G4 Dna ◽  
Selective Stabilization ◽  
G Quadruplex

Macrocyclization improves the selectivity, affinity, and ability to stabilize G4 DNA structures.

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