Identification of Novel Quadruplex Ligands from Small Molecule Libraries by FRET-Based High-Throughput Screening

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2011
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ChemBioChem ; 12 (2011), 9. - pp. 1422-1426. - ISSN 1439-4227. - eISSN 1439-7633
Abstract
Guanosine-rich nucleic acid sequences can fold into noncanonical higher order structures named G quadruplexes (GQPs). These folds are stabilized by eight Hoogsteen hydrogen bonds per tetrad and p–p stacking interactions between the tetrads.[1] Due to their stability quadruplexes occurring in promoter regions of genes [2] or at the telomeric ends of eukaryotic chromosomes have been suspected to play regulatory roles in gene expression and cell cycle control. [3] In addition, compounds binding to quadruplexes have been studied intensively because of their potential in anticancer treatment.[4] Telomeric DNA comprises thousands of double-stranded tandem repeats of the sequence d(GGGTTA)[5] and a single stranded G rich 3’ overhang of about 100–200 nucleotides.[6] During the life time of a somatic cell telomeres are permanently shortened because of the end-replication problem. At a critical length this leads to induction of cell cycle arrest or even to cell death. [7] However, in about 80–85% of all cancer cells this problem is circumvented as the telomere length is maintained by activation of telomerase,[8] an enzyme that is inactive in somatic cells. [9] By addition of telomeric repeats to the single stranded 3’ overhang, cancer cells can become immortal.[10] Several compounds have been shown to induce quadruplexes, disturbing the telomeric structure and function providing a promising anticancer treatment.
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570 Biosciences, Biology
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small molecules,human telomeres,high-throughput screening,FRET
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ISO 690BENZ, Armin, Vijay SINGH, Thomas U. MAYER, Jörg S. HARTIG, 2011. Identification of Novel Quadruplex Ligands from Small Molecule Libraries by FRET-Based High-Throughput Screening. In: ChemBioChem. 12(9), pp. 1422-1426. ISSN 1439-4227. eISSN 1439-7633. Available under: doi: 10.1002/cbic.201100094
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@article{Benz2011-06-14Ident-13689,
  year={2011},
  doi={10.1002/cbic.201100094},
  title={Identification of Novel Quadruplex Ligands from Small Molecule Libraries by FRET-Based High-Throughput Screening},
  number={9},
  volume={12},
  issn={1439-4227},
  journal={ChemBioChem},
  pages={1422--1426},
  author={Benz, Armin and Singh, Vijay and Mayer, Thomas U. and Hartig, Jörg S.}
}
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    <dcterms:abstract xml:lang="eng">Guanosine-rich nucleic acid sequences can fold into noncanonical higher order structures named G quadruplexes (GQPs). These folds are stabilized by eight Hoogsteen hydrogen bonds per tetrad and p–p stacking interactions between the tetrads.[1] Due to their stability quadruplexes occurring in promoter regions of genes [2] or at the telomeric ends of eukaryotic chromosomes have been suspected to play regulatory roles in gene expression and cell cycle control. [3] In addition, compounds binding to quadruplexes have been studied intensively because of their potential in anticancer treatment.[4] Telomeric DNA comprises thousands of double-stranded tandem repeats of the sequence d(GGGTTA)[5] and a single stranded G rich 3’ overhang of about 100–200 nucleotides.[6] During the life time of a somatic cell telomeres are permanently shortened because of the end-replication problem. At a critical length this leads to induction of cell cycle arrest or even to cell death. [7] However, in about 80–85% of all cancer cells this problem is circumvented as the telomere length is maintained by activation of telomerase,[8] an enzyme that is inactive in somatic cells. [9] By addition of telomeric repeats to the single stranded 3’ overhang, cancer cells can become immortal.[10] Several compounds have been shown to induce quadruplexes, disturbing the telomeric structure and function providing a promising anticancer treatment.</dcterms:abstract>
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