Structural and Thermodynamic Studies of the Interaction of Distamycin A with the Parallel Quadruplex Structure [d(TGGGGT)]<sub>4</sub>

Martino, Luigi; Virno, Ada; Pagano, Bruno; Virgilio, Antonella; Micco, Simone Di; Galeone, Aldo; Giancola, Concetta; Bifulco, Giuseppe; Mayol, Luciano; Randazzo, Antonio

doi:10.1021/ja075710k

Cited by 155 publications

(127 citation statements)

References 40 publications

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“…The results obtained in the present work are in good agreement with those of Randazzo and coworkers, pointing to recognition in the groove region as the major binding mode for distamycin A. [31] Furthermore, SPR studies have shown that distamycin A has poor selectivity for G-quadruplex over duplex DNA structures. [34] DODC: The binding mode of DODC remains unclear, but it has been proposed that it interacts with quadruplex DNA by groove binding, [14b] single-loop recognition, [13a] or multipoint anchorage involving grooves and loops.…”

Section: Mmq1 and Mmq3 (Mixed P-stacking/groove-binding Ligands)supporting

confidence: 90%

“…Distamycin A has been shown to interact with fourstranded parallel DNA quadruplex to form oligonucleotides. Three models have been proposed for distamycin A-quadruplex complexes, in which the ligands bind as head-to-tail dimers in the grooves, [31] on the terminal tetrad, [32] or through a dual-mode involving groove binding and tetrad stacking. [33] However, recent studies have led to a consensus that distamycin A interacts mainly by groove binding.…”

Section: Mmq1 and Mmq3 (Mixed P-stacking/groove-binding Ligands)mentioning

confidence: 99%

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Template‐Assembled Synthetic G‐Quadruplex (TASQ): A Useful System for Investigating the Interactions of Ligands with Constrained Quadruplex Topologies

Murat

Bonnet

Heyden

et al. 2010

Chemistry A European J

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A new biomolecular device for investigating the interactions of ligands with constrained DNA quadruplex topologies, using surface plasmon resonance (SPR), is reported. Biomolecular systems containing an intermolecular-like G-quadruplex motif 1 (parallel G-quadruplex conformation), an intramolecular G-quadruplex 2, and a duplex DNA 3 have been designed and developed. The method is based on the concept of template-assembled synthetic G-quadruplex (TASQ), whereby quadruplex DNA structures are assembled on a template that allows precise control of the parallel G-quadruplex conformation. Various known G-quadruplex ligands have been used to investigate the affinities of ligands for intermolecular 1 and intramolecular 2 DNA quadruplexes. As anticipated, ligands displaying a pi-stacking binding mode showed a higher binding affinity for intermolecular-like G-quadruplexes 1, whereas ligands with other binding modes (groove and/or loop binding) showed no significant difference in their binding affinities for the two quadruplexes 1 or 2. In addition, the present method has also provided information about the selectivity of ligands for G-quadruplex DNA over the duplex DNA. A numerical parameter, termed the G-quadruplex binding mode index (G4-BMI), has been introduced to express the difference in the affinities of ligands for intermolecular G-quadruplex 1 against intramolecular G-quadruplex 2. The G-quadruplex binding mode index (G4-BMI) of a ligand is defined as follows: G4-BMI=K(D)(intra)/K(D)(inter), where K(D)(intra) is the dissociation constant for intramolecular G-quadruplex 2 and K(D)(inter) is the dissociation constant for intermolecular G-quadruplex 1. In summary, the present work has demonstrated that the use of parallel-constrained quadruplex topology provides more precise information about the binding modes of ligands.

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Section: Mmq1 and Mmq3 (Mixed P-stacking/groove-binding Ligands)supporting

confidence: 90%

Section: Mmq1 and Mmq3 (Mixed P-stacking/groove-binding Ligands)mentioning

confidence: 99%

Template‐Assembled Synthetic G‐Quadruplex (TASQ): A Useful System for Investigating the Interactions of Ligands with Constrained Quadruplex Topologies

Murat

Bonnet

Heyden

et al. 2010

Chemistry A European J

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“…We chose the parallel-stranded [dTGGGGT] 4 G-quadruplex DNA structure ( Fig. 1) because (1) starting atomic coordinates of [dTGGGGT] 4 are available from X-ray crystallography, [11][12][13][14] (2) the same molecular assembly was studied by nuclear magnetic resonance (NMR) as well and presents the same G-quadruplex core arrangement, although the thymine placement differs, with evidence for T-T interactions, [15][16][17] and (3) the central guanine-rich core remains very rigid in the gas phase, [18][19][20][21] thanks to the preservation of the G-quartet hydrogen bonds and to the coordination of three 711 ammonium cations in-between the four guanine G-quartets. Only the position of thymines in the gas phase is less certain.…”

Section: Introductionmentioning

confidence: 99%

Linking molecular models with ion mobility experiments. Illustration with a rigid nucleic acid structure

D’Atri¹,

Porrini²,

Rosu³

et al. 2015

J. Mass Spectrom.

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Ion mobility spectrometry experiments allow the mass spectrometrist to determine an ion's rotationally averaged collision cross section Ω EXP . Molecular modelling is used to visualize what ion three-dimensional structure(s) is(are) compatible with the experiment. The collision cross sections of candidate molecular models have to be calculated, and the resulting Ω CALC are compared with the experimental data. Researchers who want to apply this strategy to a new type of molecule face many questions: (1) What experimental error is associated with Ω EXP determination, and how to estimate it (in particular when using a calibration for traveling wave ion guides)? (2) How to generate plausible 3D models in the gas phase? (3) Different collision cross section calculation models exist, which have been developed for other analytes than mine. Which one(s) can I apply to my systems? To apply ion mobility spectrometry to nucleic acid structural characterization, we explored each of these questions using a rigid structure which we know is preserved in the gas phase: the tetramolecular G-quadruplex [dTGGGGT] 4 , and we will present these detailed investigation in this tutorial. Additional supporting information may be found in the online version of this article at the publisher's web site.Keywords: ion mobility spectrometry; collision cross section; structure; nucleic acids; simulations; molecular modeling; gas-phase ion structure IntroductionElectrospray mass spectrometry (ESI-MS) in native conditions can preserve the structures of biomolecules and separate them according to their mass-to-charge ratios. [1,2] Ion mobility spectrometry (IMS) separates ions according to their size-to-charge ratios in the gas-phase. [3][4][5][6] Size is related to the mass (or number of atoms) and to the three-dimensional shape of a molecule. Therefore, by hyphenating IMS to mass spectrometry (IM-MS), one can sort ions according to both mass and shape. The challenge is to decipher structural information from ion mobility experiments. [7][8][9] The physical quantity characterizing the shape is the collision cross section (CCS), [10] which will be introduced in more detail in the Section on Ion mobility and collision cross sections. The present tutorial clarifies how to interpret CCS measurements in terms of three-dimensional structure for ions larger than 100 atoms extracted from the solution by electrospray ionization (ESI). The gold standard is to match CCSs experimentally obtained from IMS with CCSs calculated for modelling three-dimensional structures of the ion of interest. We will discuss the factors that can affect the precision (reproducibility) and accuracy in both the measurements and the calculations. Understanding each of these factors is crucial to interpret quantitative matches confidently and assess the meaningfulness of structural assignments.On the experimental side, we will describe the determination of CCS from traveling wave ion mobility spectrometers and from drift tube ion mobility spectrometers, with example data recorde...

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“…There are two main binding modes have been reported so far, end-stacking mode [13][14][15][16][17][18] and groove binding mode [19][20][21][22][23][24]. In both binding modes, besides the core scaffold (G-quartets), the roles of loops are also important to interaction and have been addressed in many studies [25,26].…”

mentioning

confidence: 99%

Roles of flanking sequences in the binding between unimolecular parallel-stranded G-quadruplexes and ligands

et al. 2013

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G-quadruplexes attract more and more attention in recent years. Numerous small molecules which can induce or stabilize the formation of G-quadruplexes have been investigated on the purpose of anticancer drug development. As a motif existed in physiological condition, flanking sequences are an important part of G-quadruplexes but the study on the impact of flanking sequences on (G-quadruplex)-ligand binding is rarely reported. In this paper, the effects of flanking sequences on binding affinity between a series of unimolecular parallel-stranded G-quadruplex sequences derived from c-myc oncogene promoter (termed as c-myc G-quadruplexes) and their ligands are discussed in detail. The results showed that the flanking sequences on c-myc G-quadruplexes play key roles in (G-quadruplex)-ligand interaction. When a c-myc G-quadruplex is bound to its ligands, the flanking sequences might form a binding cavity above the terminal G-quartet, which could provide a suitable site for ligands to dock in. Moreover, the bases on flanking sequences could interact with ligand through - stacking, and finally form a sandwich-stacking mode (terminal G-quartet, ligand and bases on the flanking sequence). This mode could stabilize the (G-quadruplex)-ligand complex effectively and enhance the binding affinity dramatically. However, flanking sequences are also found to exhibit steric hindrance effect which could impede the (G-quadruplex)-ligand binding. G-quadruplex

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Structural and Thermodynamic Studies of the Interaction of Distamycin A with the Parallel Quadruplex Structure [d(TGGGGT)]₄

Cited by 155 publications

References 40 publications

Template‐Assembled Synthetic G‐Quadruplex (TASQ): A Useful System for Investigating the Interactions of Ligands with Constrained Quadruplex Topologies

Template‐Assembled Synthetic G‐Quadruplex (TASQ): A Useful System for Investigating the Interactions of Ligands with Constrained Quadruplex Topologies

Linking molecular models with ion mobility experiments. Illustration with a rigid nucleic acid structure

Roles of flanking sequences in the binding between unimolecular parallel-stranded G-quadruplexes and ligands

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Structural and Thermodynamic Studies of the Interaction of Distamycin A with the Parallel Quadruplex Structure [d(TGGGGT)]4

Cited by 155 publications

References 40 publications

Template‐Assembled Synthetic G‐Quadruplex (TASQ): A Useful System for Investigating the Interactions of Ligands with Constrained Quadruplex Topologies

Template‐Assembled Synthetic G‐Quadruplex (TASQ): A Useful System for Investigating the Interactions of Ligands with Constrained Quadruplex Topologies

Linking molecular models with ion mobility experiments. Illustration with a rigid nucleic acid structure

Roles of flanking sequences in the binding between unimolecular parallel-stranded G-quadruplexes and ligands

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Structural and Thermodynamic Studies of the Interaction of Distamycin A with the Parallel Quadruplex Structure [d(TGGGGT)]₄