G-quadruplexes: selective DNA targeting for cancer therapeutics?

Miller, Kyle M.; Rodriguez, Raphaël

doi:10.1586/ecp.11.4

Cited by 35 publications

(32 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many G-rich sequences having the potential to adopt a G4 structure are associated with cellular processes. They can be found in telomeres, oncogene promoters, non-translated RNA regions, and in virus genomes [76,[84][85][86][87][88]. Therefore, they are considered as potential clinical targets for drugs to interfere with processes like telomere maintenance and function, transcription and translation regulation, cellular localization of RNAs, virus inhibition [84,85,[89][90][91][92][93][94].…”

Section: Interaction Of Porphyrins With G-quadruplex Dnamentioning

confidence: 99%

Porphyrins in complex with DNA: Modes of interaction and oxidation reactions

Pratviel

2016

Coordination Chemistry Reviews

View full text Add to dashboard Cite

Section: Interaction Of Porphyrins With G-quadruplex Dnamentioning

confidence: 99%

Porphyrins in complex with DNA: Modes of interaction and oxidation reactions

Pratviel

2016

Coordination Chemistry Reviews

View full text Add to dashboard Cite

“…In addition to the familiar duplex structure, nucleic acids can form a variety of non-canonical triplex (4,5), quadruplex (6) or i-motif (3,7,8) structures. Some of these structures have been detected in living cells (9)(10)(11) where they may play key roles in a variety of biological processes, including replication, transcription, oncogene expression, and telomere functions (11)(12)(13)(14)(15)(16)(17). Identification of ligands that selectively bind to duplex, triplex, i-motif and G-quadruplex (G4) structures is an important and challenging goal of drug discovery (12,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32).…”

Section: Introductionmentioning

confidence: 99%

“…Identification of ligands that selectively bind to duplex, triplex, i-motif and G-quadruplex (G4) structures is an important and challenging goal of drug discovery (12,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). G4 structures, in particular, have emerged as promising therapeutic targets for anti-cancer therapies (13,18,(27)(28)(29)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42). A major challenge is to identify compounds that bind specifically to one of the several possible G4 structures without binding to duplex DNA.…”

Section: Introductionmentioning

confidence: 99%

A high-throughput fluorescent indicator displacement assay and principal component/cluster data analysis for determination of ligand-nucleic acid structural selectivity

Villar‐Guerra

Gray

Trent

et al. 2017

Preprint

View full text Add to dashboard Cite

We describe a high-throughput fluorescence indicator displacement assay (HT-FID) to evaluate the affinity and the selectivity of compounds binding to different DNA structures. We validated the assay using a library of 30 well-known nucleic acid binders containing a variety chemical scaffolds. We used a combination of principal component analysis and hierarchical clustering analysis to interpret the results obtained. This analysis classified compounds based on selectivity for AT-rich, GC-rich and G4 structures. We used the FID assay as a secondary screen to test the binding selectivity of an additional 20 compounds selected from the NCI diversity set III library that were identified as G4 binders using a thermal shift assay. The results showed G4 binding selectivity for only a few of the 20 compounds.Overall, we show that this HT-FID assay, coupled with PCA and HCA, provides a useful tool for the discovery of ligands selective for particular nucleic acid structures.

show abstract

“…[10] Given the possible involvement of G-quadruplexes in a plethora of biological processes, there is scope for the development of therapeutic agents based on G-quadruplex ligands, in order to interfere with these processes in pathological situations. [15] …”

Section: Introductionmentioning

confidence: 99%

Targeting DNA G‐Quadruplexes with Helical Small Molecules

et al. 2014

Self Cite

View full text Add to dashboard Cite

We previously identified quinoline-based oligoamide helical foldamers and a trimeric macrocycle as selective ligands of DNA quadruplexes. Their helical structure may permit the targeting of the backbone loops and grooves of G-quadruplexes instead of the G-tetrads. Given the vast array of morphologies G-quadruplex structures can adopt, this may be a way to elicit sequence selective binding. Herein, we describe the design and synthesis of molecules based on macrocyclic and helically folded oligoamides. We tested their ability to interact with the human telomeric G-quadruplex and an array of promoter G-quadruplexes using Förster Resonance Energy Transfer (FRET) melting assay and single molecule FRET. Our results show that they constitute very potent ligands, comparable to the best reported in the literature. Their mode of interaction differs from that of traditional tetrad binders, opening avenues for the development of molecules specific for certain G-quadruplex conformations.

show abstract

G-quadruplexes: selective DNA targeting for cancer therapeutics?

Cited by 35 publications

References 22 publications

Porphyrins in complex with DNA: Modes of interaction and oxidation reactions

Porphyrins in complex with DNA: Modes of interaction and oxidation reactions

A high-throughput fluorescent indicator displacement assay and principal component/cluster data analysis for determination of ligand-nucleic acid structural selectivity

Targeting DNA G‐Quadruplexes with Helical Small Molecules

Contact Info

Product

Resources

About