Topologies of G-quadruplex: Biological functions and regulation by ligands

Ma, Yue; Iida, Keisuke; Nagasawa, Kazuo

doi:10.1016/j.bbrc.2019.12.103

Cited by 70 publications

(64 citation statements)

References 168 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Each set of four guanines forms a building block, usually called a G-tetrad, that are stabilized by Hoogsteen hydrogen base-pairing in physiological conditions, π–π interactions as well as in the presence of positively charged monovalent cations (usually K + and Na + ) ( Figure 1 B) [ 5 ]. G4s are highly polymorphic and can adopt a wide variety of structures based on strand molecularity and strand direction, as well as length and loop composition [ 6 ]. According to molecularity, the structures may be distinguished as intramolecular or intermolecular [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

G-Quadruplexes and Their Ligands: Biophysical Methods to Unravel G-Quadruplex/Ligand Interactions

et al. 2021

View full text Add to dashboard Cite

Progress in the design of G-quadruplex (G4) binding ligands relies on the availability of approaches that assess the binding mode and nature of the interactions between G4 forming sequences and their putative ligands. The experimental approaches used to characterize G4/ligand interactions can be categorized into structure-based methods (circular dichroism (CD), nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography), affinity and apparent affinity-based methods (surface plasmon resonance (SPR), isothermal titration calorimetry (ITC) and mass spectrometry (MS)), and high-throughput methods (fluorescence resonance energy transfer (FRET)-melting, G4-fluorescent intercalator displacement assay (G4-FID), affinity chromatography and microarrays. Each method has unique advantages and drawbacks, which makes it essential to select the ideal strategies for the biological question being addressed. The structural- and affinity and apparent affinity-based methods are in several cases complex and/or time-consuming and can be combined with fast and cheap high-throughput approaches to improve the design and development of new potential G4 ligands. In recent years, the joint use of these techniques permitted the discovery of a huge number of G4 ligands investigated for diagnostic and therapeutic purposes. Overall, this review article highlights in detail the most commonly used approaches to characterize the G4/ligand interactions, as well as the applications and types of information that can be obtained from the use of each technique.

show abstract

Section: Introductionmentioning

confidence: 99%

G-Quadruplexes and Their Ligands: Biophysical Methods to Unravel G-Quadruplex/Ligand Interactions

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Thus, the analysis described here is not only useful for structure determination but can also be applied to screen G-quadruplex variants across a broad range of conditions to optimize the design of selective molecular probes or drug candidates. 39,40 With continued improvements in experimental and was not certified by peer review) is the author/funder. All rights reserved.…”

Section: Discussionmentioning

confidence: 99%

The Polarization Dependence of 2D IR Cross-Peaks Distinguishes Parallel-Stranded and Antiparallel-Stranded DNA G-quadruplexes

Price

Wedamulla

Hill

et al. 2021

Preprint

View full text Add to dashboard Cite

Guanine-rich nucleic acid sequences have a tendency to form four-stranded non-canonical motifs known as G-quadruplexes. These motifs may adopt a wide range of structures characterized by size, strand orientation, guanine base conformation, and fold topology. Using three K+-bound model systems, we show that vibrational coupling between guanine C6=O and ring modes varies between parallel-stranded and antiparallel-stranded G-quadruplexes, and that such structures can be distinguished by comparison of polarization dependent cross-peaks in their two-dimensional infrared (2D IR) spectra. Combined with previously defined vibrational frequency trends, this analysis reveals key features of a 30-nucleotide unimolecular variant of the Bcl-2 proximal promoter that are consistent with its reported structure. This study shows that 2D IR spectroscopy is a convenient method for analyzing G-quadruplex structures that can be applied to complex sequences where traditional high-resolution methods are limited by solubility and disorder.

show abstract

“…G4s are four-stranded DNA structures formed from tetrads, consisting of guanine residues stabilized by hydrogen bonds of Hoogsteen-type [ 45 , 46 , 47 , 48 ]. G4s are polymorphic compared to dsDNA and heavily dependent on in vitro environmental conditions, under which they might adopt multiple, often coexisting, folding topologies [ 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. The structure that a given G4 adopts under in vitro conditions is not necessarily the same as that in vivo [ 34 , 40 ].…”

Section: Introductionmentioning

confidence: 99%

Towards Profiling of the G-Quadruplex Targeting Drugs in the Living Human Cells Using NMR Spectroscopy

Krafčík

Ištvánková

Džatko

et al. 2021

IJMS

View full text Add to dashboard Cite

Recently, the 1H-detected in-cell NMR spectroscopy has emerged as a unique tool allowing the characterization of interactions between nucleic acid-based targets and drug-like molecules in living human cells. Here, we assess the application potential of 1H and 19F-detected in-cell NMR spectroscopy to profile drugs/ligands targeting DNA G-quadruplexes, arguably the most studied class of anti-cancer drugs targeting nucleic acids. We show that the extension of the original in-cell NMR approach is not straightforward. The severe signal broadening and overlap of 1H in-cell NMR spectra of polymorphic G-quadruplexes and their complexes complicate their quantitative interpretation. Nevertheless, the 1H in-cell NMR can be used to identify drugs that, despite strong interaction in vitro, lose their ability to bind G-quadruplexes in the native environment. The in-cell NMR approach is adjusted to a recently developed 3,5-bis(trifluoromethyl)phenyl probe to monitor the intracellular interaction with ligands using 19F-detected in-cell NMR. The probe allows dissecting polymorphic mixture in terms of number and relative populations of individual G-quadruplex species, including ligand-bound and unbound forms in vitro and in cellulo. Despite the probe’s discussed limitations, the 19F-detected in-cell NMR appears to be a promising strategy to profile G-quadruplex–ligand interactions in the complex environment of living cells.

show abstract

Topologies of G-quadruplex: Biological functions and regulation by ligands

Cited by 70 publications

References 168 publications

G-Quadruplexes and Their Ligands: Biophysical Methods to Unravel G-Quadruplex/Ligand Interactions

G-Quadruplexes and Their Ligands: Biophysical Methods to Unravel G-Quadruplex/Ligand Interactions

The Polarization Dependence of 2D IR Cross-Peaks Distinguishes Parallel-Stranded and Antiparallel-Stranded DNA G-quadruplexes

Towards Profiling of the G-Quadruplex Targeting Drugs in the Living Human Cells Using NMR Spectroscopy

Contact Info

Product

Resources

About