Ascididemin and meridine stabilise G-quadruplexes and inhibit telomerase in vitro

Lionel Guittat; Anne De Cian; Frédéric Rosu; Valérie Gabelica; Edwin De Pauw; Evelyne Delfourne; Jean Louis Mergny

doi:10.1016/j.bbagen.2005.04.023

Ascididemin and meridine stabilise G-quadruplexes and inhibit telomerase in vitro

Lionel Guittat
, Anne De Cian
, Frédéric Rosu
, Valérie Gabelica
, Edwin De Pauw
, Evelyne Delfourne
, Jean Louis Mergny

CNRS/Museum National d'Histoire Naturelle/IRD/UPMC
University of Liège
Université Paul Sabatier

Research output: Contribution to journal › Article › peer-review

Abstract

Ascididemin and Meridine are two marine compounds with pyridoacridine skeletons known to exhibit interesting antitumour activities. These molecules have been reported to behave like DNA intercalators. In this study, dialysis competition assay and mass spectrometry experiments were used to determine the affinity of ascididemin and meridine for DNA structures among duplexes, triplexes, quadruplexes and single-strands. Our data confirm that ascididemin and meridine interact with DNA but also recognize triplex and quadruplex structures. These molecules exhibit a significant preference for quadruplexes over duplexes or single-strands. Meridine is a stronger quadruplex ligand and therefore a stronger telomerase inhibitor than ascididemin (IC₅₀ = 11 and >80 μM, respectively in a standard TRAP assay).

Original language	English
Pages (from-to)	375-384
Number of pages	10
Journal	Biochimica et Biophysica Acta - General Subjects
Volume	1724
Issue number	3
DOIs	https://doi.org/10.1016/j.bbagen.2005.04.023
Publication status	Published - 5 Aug 2005
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 14 Life Below Water

Keywords

DNA ligands
G-Quartet
G-quadruplex
Telomerase inhibitor
Telomeres

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10.1016/j.bbagen.2005.04.023

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@article{0644dc27796a4346bf2b376a1b345fb3,

title = "Ascididemin and meridine stabilise G-quadruplexes and inhibit telomerase in vitro",

abstract = "Ascididemin and Meridine are two marine compounds with pyridoacridine skeletons known to exhibit interesting antitumour activities. These molecules have been reported to behave like DNA intercalators. In this study, dialysis competition assay and mass spectrometry experiments were used to determine the affinity of ascididemin and meridine for DNA structures among duplexes, triplexes, quadruplexes and single-strands. Our data confirm that ascididemin and meridine interact with DNA but also recognize triplex and quadruplex structures. These molecules exhibit a significant preference for quadruplexes over duplexes or single-strands. Meridine is a stronger quadruplex ligand and therefore a stronger telomerase inhibitor than ascididemin (IC50 = 11 and >80 μM, respectively in a standard TRAP assay).",

keywords = "DNA ligands, G-Quartet, G-quadruplex, Telomerase inhibitor, Telomeres",

author = "Lionel Guittat and \{De Cian\}, Anne and Fr{\'e}d{\'e}ric Rosu and Val{\'e}rie Gabelica and \{De Pauw\}, Edwin and Evelyne Delfourne and Mergny, \{Jean Louis\}",

note = "Funding Information: We thank L. Lacroix, S. Amrane (MNHN, Paris, France) Patrick Mailliet and Eliane Mandine (Aventis Pharma, Vitry, France) Jean-Fran{\c c}ois Riou (Universit{\'e} de Reims) and Madhu Chauhan (University of Cape Town) for helpful discussions. V. Gabelica is a postdoctoral research fellow of the FNRS (Fonds National de la Recherche Scientifique, Belgium). This work was supported by an ARC grant (no. 3365) (to J-L.M.).",

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month = aug,

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doi = "10.1016/j.bbagen.2005.04.023",

language = "English",

volume = "1724",

pages = "375--384",

journal = "Biochimica et Biophysica Acta - General Subjects",

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TY - JOUR

T1 - Ascididemin and meridine stabilise G-quadruplexes and inhibit telomerase in vitro

AU - Guittat, Lionel

AU - De Cian, Anne

AU - Rosu, Frédéric

AU - Gabelica, Valérie

AU - De Pauw, Edwin

AU - Delfourne, Evelyne

AU - Mergny, Jean Louis

N1 - Funding Information: We thank L. Lacroix, S. Amrane (MNHN, Paris, France) Patrick Mailliet and Eliane Mandine (Aventis Pharma, Vitry, France) Jean-François Riou (Université de Reims) and Madhu Chauhan (University of Cape Town) for helpful discussions. V. Gabelica is a postdoctoral research fellow of the FNRS (Fonds National de la Recherche Scientifique, Belgium). This work was supported by an ARC grant (no. 3365) (to J-L.M.).

PY - 2005/8/5

Y1 - 2005/8/5

N2 - Ascididemin and Meridine are two marine compounds with pyridoacridine skeletons known to exhibit interesting antitumour activities. These molecules have been reported to behave like DNA intercalators. In this study, dialysis competition assay and mass spectrometry experiments were used to determine the affinity of ascididemin and meridine for DNA structures among duplexes, triplexes, quadruplexes and single-strands. Our data confirm that ascididemin and meridine interact with DNA but also recognize triplex and quadruplex structures. These molecules exhibit a significant preference for quadruplexes over duplexes or single-strands. Meridine is a stronger quadruplex ligand and therefore a stronger telomerase inhibitor than ascididemin (IC50 = 11 and >80 μM, respectively in a standard TRAP assay).

AB - Ascididemin and Meridine are two marine compounds with pyridoacridine skeletons known to exhibit interesting antitumour activities. These molecules have been reported to behave like DNA intercalators. In this study, dialysis competition assay and mass spectrometry experiments were used to determine the affinity of ascididemin and meridine for DNA structures among duplexes, triplexes, quadruplexes and single-strands. Our data confirm that ascididemin and meridine interact with DNA but also recognize triplex and quadruplex structures. These molecules exhibit a significant preference for quadruplexes over duplexes or single-strands. Meridine is a stronger quadruplex ligand and therefore a stronger telomerase inhibitor than ascididemin (IC50 = 11 and >80 μM, respectively in a standard TRAP assay).

KW - DNA ligands

KW - G-Quartet

KW - G-quadruplex

KW - Telomerase inhibitor

KW - Telomeres

U2 - 10.1016/j.bbagen.2005.04.023

DO - 10.1016/j.bbagen.2005.04.023

M3 - Article

C2 - 15950388

AN - SCOPUS:23144458156

SN - 0304-4165

VL - 1724

SP - 375

EP - 384

JO - Biochimica et Biophysica Acta - General Subjects

JF - Biochimica et Biophysica Acta - General Subjects

IS - 3

ER -

Ascididemin and meridine stabilise G-quadruplexes and inhibit telomerase in vitro

Abstract

UN SDGs

Keywords

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