UMR9187 / U1196 – Chimie et Modélisation pour la Biologie du Cancer (CMBC)

Publications de l’unité

Année de publication : 2009

Ibrahima Diallo, Nadia Haddy, Elisabeth Adjadj, Akhtar Samand, Eric Quiniou, Jean Chavaudra, Iannis Alziar, Nathalie Perret, Sylvie Guérin, Dimitri Lefkopoulos, Florent de Vathaire (2009 Apr 24)

Frequency distribution of second solid cancer locations in relation to the irradiated volume among 115 patients treated for childhood cancer.

International journal of radiation oncology, biology, physics : 74 : 876-883 : DOI : 10.1016/j.ijrobp.2009.01.040 En savoir plus
Résumé

PURPOSE:

To provide better estimates of the frequency distribution of second malignant neoplasm (SMN) sites in relation to previous irradiated volumes, and better estimates of the doses delivered to these sites during radiotherapy (RT) of the first malignant neoplasm (FMN).

METHODS AND MATERIALS:

The study focused on 115 patients who developed a solid SMN among a cohort of 4581 individuals. The homemade software package Dos_EG was used to estimate the radiation doses delivered to SMN sites during RT of the FMN. Three-dimensional geometry was used to evaluate the distances between the irradiated volume, for RT delivered to each FMN, and the site of the subsequent SMN.

RESULTS:

The spatial distribution of SMN relative to the irradiated volumes in our cohort was as follows: 12% in the central area of the irradiated volume, which corresponds to the planning target volume (PTV), 66% in the beam-bordering region (i.e., the area surrounding the PTV), and 22% in regions located more than 5 cm from the irradiated volume. At the SMN site, all dose levels ranging from almost zero to >75 Gy were represented. A peak SMN frequency of approximately 31% was identified in volumes that received <2.5 Gy.

CONCLUSION:

A greater volume of tissues receives low or intermediate doses in regions bordering the irradiated volume with modern multiple-beam RT arrangements. These results should be considered for risk-benefit evaluations of RT.

Replier
Peng Yang, Anne De Cian, Marie-Paule Teulade-Fichou, Jean-Louis Mergny, David Monchaud (2009 Mar 9)

Engineering bisquinolinium/thiazole orange conjugates for fluorescent sensing of G-quadruplex DNA.

Angewandte Chemie (International ed. in English) : 48 : 2188-2191 : DOI : 10.1002/anie.200805613 En savoir plus
Résumé

Lighting up: A G-quadruplex-specific fluorescent probe was designed combining the specificity of the pyridodicarboxamide motif for guanine quadruplexes and the fluorescence properties of thiazole orange. While the assembly of the two partners through a flexible linker leads to a nonselective probe, merging them in a single, rigid scaffold leads to a dye that elicits the properties required for G-quadruplex sensing.

Replier
Anton Granzhan, Marie-Paule Teulade-Fichou (2009 Jan 26)

A fluorescent bisanthracene macrocycle discriminates between matched and mismatch-containing DNA.

Chemistry (Weinheim an der Bergstrasse, Germany) : 15 : 1314-1318 : DOI : 10.1002/chem.200802421 En savoir plus
Résumé

Mix and measure: A fluorescent bisanthracene macrocycle binds to fully matched and thymine‐mismatched (TX) DNA duplexes by different binding modes, which may be differentiated spectroscopically. This behavior allows an easy fluorimetric or “naked‐eye” discrimination between matched (X=A) and mismatch‐containing (X=C, T, or G) oligonucleotides.

Replier
Liliane Mouawad, Adriana Isvoran, Eric Quiniou, Constantin T Craescu (2009 Jan 22)

What determines the degree of compactness of a calcium-binding protein?

The FEBS journal : 276 : 1082-1093 : DOI : 10.1111/j.1742-4658.2008.06851.x En savoir plus
Résumé

The EF-hand calcium-binding proteins may exist either in an extended or a compact conformation. This conformation is sometimes correlated with the function of the calcium-binding protein. For those proteins whose structure and function are known, calcium sensors are usually extended and calcium buffers compact; hence, there is interest in predicting the form of the protein starting from its sequence. In the present study, we used two different procedures: one that already exists in the literature, the sosuidumbbell algorithm, mainly based on the charges of the two EF-hand domains, and the other comprising a novel procedure that is based on linker average hydrophilicity. The linker consists of the residues that connect the domains. The two procedures were tested on 17 known-structure calcium-binding proteins and then applied to 59 unknown-structure centrins. The sosuidumbbell algorithm yielded the correct conformations for only 15 of the known-structure proteins and predicted that all centrins should be in a closed form. The linker average hydrophilicity procedure discriminated well between all the extended and non-extended forms of the known-structure calcium-binding proteins, and its prediction concerning centrins reflected well their phylogenetic classification. The linker average hydrophilicity criterion is a simple and powerful means to discriminate between extended and non-extended forms of calcium-binding proteins. What is remarkable is that only a few residues that constitute the linker (between 2 and 20 in our tested sample of proteins) are responsible for the form of the calcium-binding protein, showing that this form is mainly governed by short-range interactions.

Replier

Année de publication : 2008

Guillaume Bordeau, Rémy Lartia, Germain Metge, Céline Fiorini-Debuisschert, Fabrice Charra, Marie-Paule Teulade-Fichou (2008 Nov 19)

Trinaphthylamines as robust organic materials for two-photon-induced fluorescence.

Journal of the American Chemical Society : 130 : 16836-16837 : DOI : 10.1021/ja8055112 En savoir plus
Résumé

The synthesis of a novel π-conjugated trinaphthylamines series is described. These original push−pull octupolar systems exhibit large two-photon action cross section (σϕ up to 510 GM) increased by a factor of 2−3 as compared to their triphenylamines analogues. This substantial improvement of the two-photon absorption properties is attributed to the stronger donor character of the trinaphthyl core.

Replier
Anne De Cian, Philippe Grellier, Elisabeth Mouray, Delphine Depoix, Hélène Bertrand, David Monchaud, Marie-Paule Teulade-Fichou, Jean-Louis Mergny, Patrizia Alberti (2008 Nov 3)

Plasmodium telomeric sequences: structure, stability and quadruplex targeting by small compounds.

Chembiochem : a European journal of chemical biology : 9 : 2730-2739 : DOI : 10.1002/cbic.200800330 En savoir plus
Résumé

The increasing resistance of Plasmodium falciparum to the most commonly used antimalarial drugs makes it necessary to identify new therapeutic targets. The telomeres of the parasite could constitute an attractive target. They are composed of repetitions of a degenerate motif ((5′)GGGTTYA(3′), where Y is T or C), different from the human one ((5′)GGGTTA(3′)). In this report we investigate the possibility of targeting Plasmodium telomeres with G-quadruplex ligands. Through solution hybridisation assays we provide evidence of the existence of a telomeric 3′ G-overhang in P. falciparum genomic DNA. Through UV spectroscopy studies we demonstrate that stable G-quadruplex structures are formed at physiological temperature by sequences composed of the degenerate Plasmodium telomeric motif. Through a FRET melting assay we show stabilisation of Plasmodium telomeric G-quadruplexes by a variety of ligands. Many of the tested ligands display strong quadruplex versus duplex selectivity, but show little discrimination between human and Plasmodium telomeric quadruplexes.

Replier
Anja Henn, Astrid Joachimi, Diana P N Gonçalves, David Monchaud, Marie-Paule Teulade-Fichou, Jeremy K M Sanders, Jörg S Hartig (2008 Nov 3)

Inhibition of dicing of guanosine-rich shRNAs by quadruplex-binding compounds.

Chembiochem : a European journal of chemical biology : 9 : 2722-2729 : DOI : 10.1002/cbic.200800271 En savoir plus
Résumé

RNA interference is triggered by small hairpin precursors that are processed by the endonuclease dicer to yield active species such as siRNAs and miRNAs. To regulate the RNAi-mediated suppression of gene expression, we imagined a strategy that relies on the sequence-specific inhibition of shRNA precursor processing by immediate RNA-small molecule interactions. Here, we present a first step in this direction by augmenting shRNAs with guanosine-rich sequences that are prone to fold into four-stranded structures. The addition of small molecules that selectively bind to such quadruplex sequences should allow for the specific inhibition of dicing of shRNAs that contain suitable G-rich elements. In an attempt to find compounds that protect against dicer processing, we have examined the effects of quadruplex-binding compounds on the dicer processing of shRNAs containing G-quadruplexes. Although a variety of small molecules that are known to bind to quadruplexes inhibited in vitro dicing of shRNAs, only two substance classes, namely certain porphyrazines and bisquinolinium compounds, showed selective inhibition of G-rich shRNAs compared to control sequences lacking guanine-rich elements. The G-rich shRNAs displayed a potent knockdown of gene expression in mammalian cell culture, but the effect was not influenced by addition of the respective quadruplex-binding compounds.

Replier
Hélène Bertrand, Sophie Bombard, David Monchaud, Marie-Paule Teulade-Fichou (2008 Sep 1)

New platinum(II) complexes targeting the loops of the human telomeric G-quadruplex.

Nucleic acids symposium series (2004) : 52 : 163-164 : DOI : 10.1093/nass/nrn083 En savoir plus
Résumé

Two novel series of platinum(II) complexes have been designed and shown to interact with the human telomeric G-quadruplex-DNA via different binding modes: i- terpyridine-platinum (Pt-tpy) complexes covalently interact with quadruplex-DNA via selective platination of adenine residues of the loops, their interaction being driven by the aromatic surface of the ligand; ii- platinum-quinacridine hybrid (Pt-MPQ) interacts with quadruplex-DNA via a dual noncovalent/covalent binding mode, targeting preferentially guanines constitutive of external G-quartets. Therefore, platinum complexes presented herein constitute potential agents for irreversible trapping of G-quadruplex.DNA.

Replier
G Bordeau, E Faurel, C Allain, R Lartia, F Schmidt, C Fiorini-Debuisschert, F Charra, G Metge, P Tauc, M-P Teulade-Fichou (2008 Sep 1)

New triarylamine-based far-red DNA stainers with high two-photon absorption properties.

Nucleic acids symposium series (2004) : 52 : 155-156 : DOI : 10.1093/nass/nrn079 En savoir plus
Résumé

A series of red emitting vinyl-triphenyamines (TP) have been synthesized and evaluated for their two photon absorption (2PA) properties. These compounds are virtually non fluorescent in the free state but exhibit a bright red fluorescence upon binding to double-stranded DNA, both in one- and two-photon absorption. This feature allows one- and two-photon confocal imaging in cells of nuclear DNA with an excellent contrast. Derivatizable analogues for covalent bioconjugation to oligonucleotides are described and variation on the structure is discussed.

Replier
Matthias Bahr, Valerie Gabélica, Anton Granzhan, Elmar Weinhold, Marie-Paule Teulade-Fichou (2008 Sep 1)

Recognition of homopyrimidine mismatches by distance-constrained macrocyclic bisintercalators.

Nucleic acids symposium series (2004) : 52 : 109-110 : DOI : 10.1093/nass/nrn056 En savoir plus
Résumé

Binding of three macrocyclic bisintercalators to mismatch-containing duplexes was analyzed by thermal denaturation experiments, electrospray mass spectrometry studies (ESI-MS) and fluorescent intercalator displacement (FID) titrations. The macrocyclic bisintercalators bind to duplexes containing mismatched thymine bases with high selectivity over the fully matched one and affinity in the submicromolar range (Kd). The FID results also demonstrate that the macrocyclic naphthalene derivative BisNP preferentially binds to pyrimidine-pyrimidine mismatches compared to all other possible base mismatches. This ligand also efficiently competes with a DNA enzyme (M.TaqI) for binding to a duplex with a TT-mismatch.

Replier
Matthias Bahr, Valérie Gabelica, Anton Granzhan, Marie-Paule Teulade-Fichou, Elmar Weinhold (2008 Sep 1)

Selective recognition of pyrimidine-pyrimidine DNA mismatches by distance-constrained macrocyclic bis-intercalators.

Nucleic acids research : 36 : 5000-5012 : DOI : 10.1093/nar/gkn392 En savoir plus
Résumé

Binding of three macrocyclic bis-intercalators, derivatives of acridine and naphthalene, and two acyclic model compounds to mismatch-containing and matched duplex oligodeoxynucleotides was analyzed by thermal denaturation experiments, electrospray ionization mass spectrometry studies (ESI-MS) and fluorescent intercalator displacement (FID) titrations. The macrocyclic bis-intercalators bind to duplexes containing mismatched thymine bases with high selectivity over the fully matched ones, whereas the acyclic model compounds are much less selective and strongly bind to the matched DNA. Moreover, the results from thermal denaturation experiments are in very good agreement with the binding affinities obtained by ESI-MS and FID measurements. The FID results also demonstrate that the macrocyclic naphthalene derivative BisNP preferentially binds to pyrimidine-pyrimidine mismatches compared to all other possible base mismatches. This ligand also efficiently competes with a DNA enzyme (M.TaqI) for binding to a duplex with a TT-mismatch, as shown by competitive fluorescence titrations. Altogether, our results demonstrate that macrocyclic distance-constrained bis-intercalators are efficient and selective mismatch-binding ligands that can interfere with mismatch-binding enzymes.

Replier
Besselièvre F., Piguel S., Mahuteau-Betzer F., Grierson D.S. (2008 Aug 23)

Stereoselective Direct Copper-Catalyzed Alkenylation of Oxazoles with Bromoalkenes

Organic Letters : 10 : 4029-4032 : DOI : 10.1021/ol801512q En savoir plus
Résumé

A copper-catalyzed direct alkenylation of oxazoles with bromoalkenes has been developed. The method is both regio- and stereoselective and tolerates a variety of functional groups. A wide range of 2-E-vinyl-substituted oxazoles were obtained in high yields including the highly fluorescent alkaloid annuloline.

Replier
D Monchaud, C Allain, H Bertrand, N Smargiasso, F Rosu, V Gabelica, A De Cian, J-L Mergny, M-P Teulade-Fichou (2008 Aug 1)

Ligands playing musical chairs with G-quadruplex DNA: a rapid and simple displacement assay for identifying selective G-quadruplex binders.

Biochimie : 90 : 1207-1223 : DOI : 10.1016/j.biochi.2008.02.019 En savoir plus
Résumé

We report here the details of G4-FID (G-quadruplex fluorescent intercalator displacement), a simple method aiming at evaluating quadruplex-DNA binding affinity and quadruplex- over duplex-DNA selectivity of putative ligands. This assay is based on the loss of fluorescence upon displacement of thiazole orange from quadruplex- and duplex-DNA matrices. The original protocol was tested using various quadruplex- and duplex-DNA targets, and with a wide panel of G-quadruplex ligands belonging to different families (i.e. from quinacridines to metallo-organic ligands) likely to display various binding modes. The reliability of the assay is further supported by comparisons with FRET-melting and ESI-MS assays.

Replier
David Monchaud, Peng Yang, Laurent Lacroix, Marie-Paule Teulade-Fichou, Jean-Louis Mergny (2008 Jun 16)

A metal-mediated conformational switch controls G-quadruplex binding affinity.

Angewandte Chemie (International ed. in English) : 47 : 4858-4861 : DOI : 10.1002/anie.200800468 En savoir plus
Résumé

Control by copper: CuII ions modulate the quadruplex affinity of the high‐affinity ligand 360A and denaturate the folded quadruplex form of DNA 22AG to an unfolded form. So removal of copper through complexation enables the cycling of both 360A quadruplex affinity and quadruplex unfolding.

Replier
Samir Amrane, Anne De Cian, Frédéric Rosu, Markus Kaiser, Edwin De Pauw, Marie-Paule Teulade-Fichou, Jean-Louis Mergny (2008 May 23)

Identification of trinucleotide repeat ligands with a FRET melting assay.

Chembiochem : a European journal of chemical biology : 9 : 1229-1234 : DOI : 10.1002/cbic.200800062 En savoir plus
Résumé

DNA hairpin structures formed within a repeated tract might be a causative factor for triplet expansion observed in several debilitating diseases. We have designed and used a fluorescence resonance energy transfer (FRET) melting assay to screen for ligands that bind specifically to the CNG triplet repeats. Using this assay, we screened a panel of 33 chemicals that were previously designed to bind DNA or RNA secondary structures. Remarkably, we found that macrocyclic compounds, such as acridine dimers and trimers, exhibit interesting affinities and specificities for this motif.

Replier