scholarly journals Specific Stabilization of c-MYC and c-KIT G-Quadruplex DNA Structures by Indolylmethyleneindanone Scaffolds

Biochemistry ◽  
2016 ◽  
Vol 55 (25) ◽  
pp. 3571-3585 ◽  
Author(s):  
K. V. Diveshkumar ◽  
Saaz Sakrikar ◽  
Frédéric Rosu ◽  
S. Harikrishna ◽  
Valérie Gabelica ◽  
...  
Keyword(s):  
Quadruplex Dna ◽  
Dna Structures ◽  
G Quadruplex

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 G-Quadruplex Dna Structures And Site Specific Genetic Instability

2015 ◽  
Author(s):  
Jonathan David Williams
Keyword(s):  
Genetic Instability ◽  
Site Specific ◽  
Quadruplex Dna ◽  
Dna Structures ◽  
G Quadruplex

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 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.

Design and Synthesis of 2,2′-Diindolylmethanes to Selectively Target Certain G-Quadruplex DNA Structures

2016 ◽  
Vol 22 (37) ◽  
pp. 13004-13009 ◽  
Author(s):  
Madeleine Livendahl ◽  
Jan Jamroskovic ◽  
Svetlana Ivanova ◽  
Peter Demirel ◽  
Nasim Sabouri ◽  
...  
Keyword(s):  
Quadruplex Dna ◽  
Dna Structures ◽  
Design And Synthesis ◽  
G Quadruplex

scholarly journals Repair of O6-methylguanine adducts in human telomeric G-quadruplex DNA by O6-alkylguanine-DNA alkyltransferase

2014 ◽  
Vol 42 (15) ◽  
pp. 9781-9791 ◽  
Author(s):  
Lance M. Hellman ◽  
Tyler J. Spear ◽  
Colton J. Koontz ◽  
Manana Melikishvili ◽  
Michael G. Fried
Keyword(s):  
Conformational Dynamics ◽  
Rapid Phase ◽  
Quadruplex Dna ◽  
Dna Structures ◽  
Ability To Act ◽  
Telomere Sequence ◽  
G Quadruplex ◽  
Dna Alkyltransferase ◽  
Quadruplex Formation ◽  
Dna Substrate

Abstract O 6-alkylguanine-DNA alkyltransferase (AGT) is a single-cycle DNA repair enzyme that removes pro-mutagenic O6-alkylguanine adducts from DNA. Its functions with short single-stranded and duplex substrates have been characterized, but its ability to act on other DNA structures remains poorly understood. Here, we examine the functions of this enzyme on O6-methylguanine (6mG) adducts in the four-stranded structure of the human telomeric G-quadruplex. On a folded 22-nt G-quadruplex substrate, binding saturated at 2 AGT:DNA, significantly less than the ∼5 AGT:DNA found with linear single-stranded DNAs of similar length, and less than the value found with the telomere sequence under conditions that inhibit quadruplex formation (4 AGT:DNA). Despite these differences, AGT repaired 6mG adducts located within folded G-quadruplexes, at rates that were comparable to those found for a duplex DNA substrate under analogous conditions. Repair was kinetically biphasic with the amplitudes of rapid and slow phases dependent on the position of the adduct within the G-quadruplex: in general, adducts located in the top or bottom tetrads of a quadruplex stack exhibited more rapid-phase repair than did adducts located in the inner tetrad. This distinction may reflect differences in the conformational dynamics of 6mG residues in G-quadruplex DNAs.

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