A hitchhiker's guide to G-quadruplex ligands

Monchaud, David; Teulade-Fichou, Marie-Paule

doi:10.1039/b714772b

Cited by 744 publications

(581 citation statements)

References 199 publications

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“…The formation and/or stabilization of G-quadruplexes by selective small molecules, so-called G-quadruplexes ligands (stabilizers) appear as a novel therapeutic strategy to control those key cellular events. [269,272,273] Most of the molecules reported to date as quadruplex DNA stabilisers/binders are based on large organic heteroaromatic systems. However, a number of metal complexes have also been designed to bind and as potentially inhibiting telomerase activity.…”

Section: Dna G-quadruplexesmentioning

confidence: 99%

“…[269] G-quadruplexes (G4s) are specific architectures of nucleic acids adopted by guanine-rich DNA and RNA sequences, whose stability comes from the stacking of contiguous G-quartets (planar and cyclic association of four guanine residues mediated by a central potassium or sodium ion in a Hoogsteen H-bonding arrangement). [270] G-quadruplexes are currently widely studied as they are suspected to play a crucial role in key cellular mechanisms.…”

Section: Dna G-quadruplexesmentioning

confidence: 99%

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Mass spectrometry as a powerful tool to study therapeutic metallodrugs speciation mechanisms: Current frontiers and perspectives

Wenzel

Casini

2017

Coordination Chemistry Reviews

108

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Metal-based compounds form a promising class of therapeutic agents, whose mechanisms of action still need to be elucidated, and that are in general prone to undergo extensive speciation in physiological environment. Thus, determination of the fate of the metal compounds in complex biological systems, contributing to their overall pharmacological and toxicological profiles, is important to develop more rationalised and targeted metal-based drugs. To these aims, a number of spectroscopic and biophysical methods, as well as analytical techniques, are nowadays extensively applied to study the reactivity of metal complexes with different biomolecules (e.g. nucleic acids, proteins, buffer components). Among the various techniques, molecular mass spectrometry (MS) has emerged in the last decade as a major tool to characterise the interactions of metallodrugs at a molecular level. In this review, we present an overview of the information available on the reactivity of various families of therapeutic metallodrugs (mainly anticancer compounds based on Pt, Ru, Au and As) with biomolecules studied by different MS techniques, including high-resolution ESI-, MALDI-and ion mobility-MS among others. Representative examples on the potential of the MS approach to study non-covalent interactions are also discussed. The review is organized to present results obtained on samples with different degrees of complexity, from the interactions of metal compounds with small model nucleophiles (amino acids and nucleobases), model peptides/oligonucleotides, target proteins/nucleic acids, to the analysis of serum, cell extracts and tissue samples. The latter requiring combination of proteomic methods with advanced MS techniques. Correlations between molecular reactivity of metallodrugs and biological activity are hard to establish, but differences in the reactivity of metallodrugs to biomolecules and their different adducts, as revealed by MS methods, may indicate differences in their modes of action. Overall, the knowledge offered by MS methods on metallodrugs speciation is invaluable to establish new rules and define new trends in the periodic table aimed at rationalizing the behavior of metal compounds in complex living systems. Keywordsmetal-based drugs; proteins; nucleic acids; mass spectrometry; metallomics. Corresponding Author Angela Casini Corresponding Author's InstitutionCardiff University To view all the submission files, including those not included in the PDF, click on the manuscript title on your EVISE Homepage, then click 'Download zip file'. Order of Authors 1 Answers to Reviewers Reviewer 1 The authors have made some effort to answer suggestions and the manuscript is improved. Since it is a review, there is, strictly, no new information but nevertheless the compilation of data and references could be useful.Answer: no further comments. Liu et al." in place of "Lu et al." iv) Some symbols in the PDF file are not correctly displayed. Reviewer Answer:We have inserted all the minor modifications requested by this rev...

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Section: Dna G-quadruplexesmentioning

confidence: 99%

Section: Dna G-quadruplexesmentioning

confidence: 99%

Mass spectrometry as a powerful tool to study therapeutic metallodrugs speciation mechanisms: Current frontiers and perspectives

Wenzel

Casini

2017

Coordination Chemistry Reviews

108

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“…G-quadruplexes that exist as a dynamic mixture of conformations in the unbound state, like the human telomeric sequence, [91] should generally exhibit lower ligand affinities as compared to G-quadruplexes that adopt a single conformation. [58,90] While a large number of G-quadruplex ligands have been reported in the literature, [41,42,46,89,[92][93][94] the cationic porphyrin TMPyP4 (Fig. 5) is the most extensively studied to date.…”

Section: Some Known G-quadruplex Ligands and Their Activitiesmentioning

confidence: 99%

“…[20,88,89] The most common is co-facial end-stacking or 'hemi intercalation' of the ligand onto one or both of the terminal G-tetrads. Other binding sites are defined by the surface features of the grooves and/or loop regions.…”

Section: Some Known G-quadruplex Ligands and Their Activitiesmentioning

confidence: 99%

Targeting G-Quadruplex DNA with Small Molecules

Luedtke¹

2009

Chimia

101

105

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Despite a recent explosion of interest in G-quadruplex DNA, most fundamental questions regarding the possible presence and function of these intriguing structures in vivo remain unanswered. Cell-permeable G-quadruplex specific probes should provide researchers with new tools for studying these alternately folded DNA structures and their potential involvement in gene expression, chromosome stability, viral integration, and recombination. In this review, a survey of the binding affinity, specificity, and biological/pharmacological activities of some well-characterized G-quadruplex ligands is presented along with the potential importance of G-quadruplex DNA in vivo.134 CHIMIA 2009, 63, No. 3 Young AcAdemics in switzerlAnd PArt ii doi:10.2533doi:10. /chimia.2009doi:10. .134 Chimia 63 (2009 Despite a recent explosion of interest in G-quadruplex DNA, most fundamental questions regarding the possible presence and function of these intriguing structures in vivo remain unanswered. Cell-permeable Gquadruplex specific probes should provide researchers with new tools for studying these alternately folded DNA structures and their potential involvement in gene expression, chromosome stability, viral integration, and recombination. In this review, a survey of the binding affinity, specificity, and biological/pharmacological activities of some well-characterized G-quadruplex ligands is presented along with the potential importance of G-quadruplex DNA in vivo.

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“…is the presence of an extended aromatic ring system that allows binding through π-π overlap of terminal G-tetrads. Some examples of GQ-stacking ligands are the alkylamine substituted acridines developed by Neidle (e.g., BRACO-19, with anti-cancer activity by stabilizing the telomer of human uterus carcinoma) [3,8], the perylene diimide (PIPER, stacks on the terminal G-tetrad of the human telomer) and the fluoroquinolone (quarfloxin, in phase-II clinical trials for treatment of neuroendocrine tumors by targeting GQ-cMyc gene promoter) derivatives prepared by Hurley and coworkers [13], the naphtalenediimides reported by Neidle and Hartley (MM 41 , with antitumor activity against pancreatic cancer) [3,8], or the dibenzophenanthrolines (e.g., MMQ 3 ) and bisquinolinium derivatives (Phen-DC6, high affinity GQ ligand) developed by TeuladeFichou and Mergny [3,14]. Although generally flat aromatic molecules stacking on G-tetrads show higher binding constants than non-planar systems, planarity by itself is insufficient for high-affinity and unlikely to confer selectivity.…”

mentioning

confidence: 99%