ESI-MS Investigation of an Equilibrium between a Bimolecular Quadruplex DNA and a Duplex DNA/RNA Hybrid

Birrento, Monica L.; Bryan, Tracy M.; Samosorn, Siritron; Beck, Jennifer L.

doi:10.1007/s13361-015-1121-2

Cited by 8 publications

(11 citation statements)

References 36 publications

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“…For telomerase, we favour a model in which the enzyme binds the G4 while it is still structured, followed by invasion by the RNA template; confirmation of this model will require further kinetic analyses. A similar template-mimicking RNA was unable to form a DNA-RNA hybrid with an antiparallel G4 of similar stability to the parallel G4 used in the present study ( Birrento et al, 2015 ), demonstrating that this is a specific interaction between this RNA and parallel G4 structures. Single-molecule FRET studies have illuminated the mechanisms used by other G4-unwinding proteins; for example, the helicase RHAU/DHX36 was shown to stack on the top of the G4 plane and bind to the exposed 3' single stranded DNA tail ( Chen et al, 2018 ), whereas the replication protein RPA has been proposed to bind to G4 structures via their exposed loops ( Ray et al, 2013 ).…”

Section: Discussionsupporting

confidence: 45%

A mechanism for the extension and unfolding of parallel telomeric G-quadruplexes by human telomerase at single-molecule resolution

Paudel

Moye

Assi

et al. 2020

eLife

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Telomeric G-quadruplexes (G4) were long believed to form a protective structure at telomeres, preventing their extension by the ribonucleoprotein telomerase. Contrary to this belief, we have previously demonstrated that parallel-stranded conformations of telomeric G4 can be extended by human and ciliate telomerase. However, a mechanistic understanding of the interaction of telomerase with structured DNA remained elusive. Here, we use single-molecule fluorescence resonance energy transfer (smFRET) microscopy and bulk-phase enzymology to propose a mechanism for the resolution and extension of parallel G4 by telomerase. Binding is initiated by the RNA template of telomerase interacting with the G-quadruplex; nucleotide addition then proceeds to the end of the RNA template. It is only through the large conformational change of translocation following synthesis that the G-quadruplex structure is completely unfolded to a linear product. Surprisingly, parallel G4 stabilization with either small molecule ligands or by chemical modification does not always inhibit G4 unfolding and extension by telomerase. These data reveal that telomerase is a parallel G-quadruplex resolvase.

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Section: Discussionsupporting

confidence: 45%

A mechanism for the extension and unfolding of parallel telomeric G-quadruplexes by human telomerase at single-molecule resolution

Paudel

Moye

Assi

et al. 2020

eLife

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“…Valuable information is gathered quickly with regards to preferential binding of a ligand to DNA. Although several of the studies described later will focus primarily on the binding of small molecule ligands to DNA, this technique is not limited to these specific interactions and can be applicable to other biomolecules of interest, including proteins [ 2 , 22 , 35 , 36 , 37 , 38 ], carbohydrates [ 39 , 40 ], and other types of nucleic acids such as RNA [ 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ] and peptide nucleic acids [ 52 , 53 , 54 ].…”

Section: Introductionmentioning

confidence: 99%

May the Best Molecule Win: Competition ESI Mass Spectrometry

Laughlin

Wilson

2015

IJMS

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Electrospray ionization mass spectrometry has become invaluable in the characterization of macromolecular biological systems such as nucleic acids and proteins. Recent advances in the field of mass spectrometry and the soft conditions characteristic of electrospray ionization allow for the investigation of non-covalent interactions among large biomolecules and ligands. Modulation of genetic processes through the use of small molecule inhibitors with the DNA minor groove is gaining attention as a potential therapeutic approach. In this review, we discuss the development of a competition method using electrospray ionization mass spectrometry to probe the interactions of multiple DNA sequences with libraries of minor groove binding molecules. Such an approach acts as a high-throughput screening method to determine important information including the stoichiometry, binding mode, cooperativity, and relative binding affinity. In addition to small molecule-DNA complexes, we highlight other applications in which competition mass spectrometry has been used. A competitive approach to simultaneously investigate complex interactions promises to be a powerful tool in the discovery of small molecule inhibitors with high specificity and for specific, important DNA sequences.

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“…It should be noted however that the situation with regard to telomerase inhibition by G-quadruplex DNA ligands has been re-evaluated and many may not be simple telomerase inhibitors. 10,11) A promising berberine-derived anticancer agent, 13-(2naphthylmethoxy) berberine bromide (1) (Fig. 1), was developed by us 12) and has been reported to have selective interaction with model G-quadruplex (G4) DNA structures over duplex DNA analogues, 11) as well as partially inhibiting telomerase unfolding and extension of an intramolecular parallel G4.…”

Section: Introductionmentioning

confidence: 99%

Enhancing Anticancer Potency of a 13-Substituted Berberine Derivative with Cationic Liposomes

Apiratikul

Sriklung

Dolsophon

et al. 2022

CHEMICAL & PHARMACEUTICAL BULLETIN

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Cationic liposomal formulations of the telomeric G-quadruplex stabilizing ligand, 13-(2-naphthylmethoxy)berberine bromide (1), have been developed with the purpose of delivering 1 into the nucleus of cancer cells for potential telomere targeting. Berberine derivative 1 was encapsulated in various cationic lipids 2-4 by the thin film evaporation method; these lipids are cationic after amine protonation. The most appropriate liposomal berberine formulation was that of 1 and the cholesterol derived cationic lipid 4 in a weight ratio of 1 : 20 with 76.5% encapsulation efficiency of 1. Cellular uptake studies in the HeLa and HT-29 cancer cells lines showed that the liposomal berberine derivative uptake in the cells was higher and more stable than for berberine derivative 1 alone while free 1 was completely decomposed in the cells within 60 min exposure to the cells. Anticancer activity of the liposomal berberine derivative 1 based on 4 was greater than that for the free berberine derivative 1 in the MCF-7, HeLa and HT-29 cell line by 2.3-, 4.9-and 5.3-fold, respectively, and also, interestingly, superior to the anticancer drug doxorubicin against the HT29 cancer cell line.

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ESI-MS Investigation of an Equilibrium between a Bimolecular Quadruplex DNA and a Duplex DNA/RNA Hybrid

Cited by 8 publications

References 36 publications

A mechanism for the extension and unfolding of parallel telomeric G-quadruplexes by human telomerase at single-molecule resolution

A mechanism for the extension and unfolding of parallel telomeric G-quadruplexes by human telomerase at single-molecule resolution

May the Best Molecule Win: Competition ESI Mass Spectrometry

Enhancing Anticancer Potency of a 13-Substituted Berberine Derivative with Cationic Liposomes

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