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Targeting human telomeric G-quadruplex DNA and inhibition of telomerase activity with [(dmb)2Ru(obip)Ru(dmb)2](4+)

Inhibition of telomerase by inducing/stabilizing G-quadruplex formation is a promising strategy to design new anticancer drugs. We synthesized and characterized a new dinuclear complex [(dmb).sub.2 Ru(obip)Ru(dmb).sub.2 ].sup.4+ (dmb = 4,4'-dimethyl-2,2'-bipyridine, obip = (2-(2-pyridyl)imidazo[4,5-... Full description

Journal Title: PLoS ONE 01 January 2013, Vol.8(12), p.e84419
Main Author: Shuo Shi
Other Authors: Shane Gao , Tongcheng Cao , Jie Liu , Xing Gao , Jian Hao , Chunyan Lv , Hailiang Huang , Jun Xu , Tianming Yao
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0084419
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recordid: doaj_soai_doaj_org_article_0c38baa91a6749d7b158378e0fcd9c89
title: Targeting human telomeric G-quadruplex DNA and inhibition of telomerase activity with [(dmb)2Ru(obip)Ru(dmb)2](4+)
format: Article
creator:
  • Shuo Shi
  • Shane Gao
  • Tongcheng Cao
  • Jie Liu
  • Xing Gao
  • Jian Hao
  • Chunyan Lv
  • Hailiang Huang
  • Jun Xu
  • Tianming Yao
subjects:
  • Sciences (General)
ispartof: PLoS ONE, 01 January 2013, Vol.8(12), p.e84419
description: Inhibition of telomerase by inducing/stabilizing G-quadruplex formation is a promising strategy to design new anticancer drugs. We synthesized and characterized a new dinuclear complex [(dmb).sub.2 Ru(obip)Ru(dmb).sub.2 ].sup.4+ (dmb = 4,4'-dimethyl-2,2'-bipyridine, obip = (2-(2-pyridyl)imidazo[4,5-f][1,10]phenanthroline) with high affinity for both antiparallel and mixed parallel / antiparallel G-quadruplex DNA. This complex can promote the formation and stabilize G-quadruplex DNA. Dialysis and TRAP experiments indicated that [(dmb).sub.2 Ru(obip)Ru(dmb).sub.2 ].sup.4+ acted as an excellent telomerase inhibitor due to its obvious selectivity for G-quadruplex DNA rather than double stranded DNA. In vitro co-culture experiments implied that [(dmb).sub.2 Ru(obip)Ru(dmb).sub.2 ].sup.4+ inhibited telomerase activity and hindered cancer cell proliferation without side effects to normal fibroblast cells. TUNEL assay indicated that inhibition of telomerase activity induced DNA cleavage further apoptosis in cancer cells. Therefore, Ru.sup.II complex represents an exciting opportunity for anticancer drug design by specifically targeting cancer cell G-quadruplexes DNA.
language: eng
source:
identifier: E-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0084419
fulltext: fulltext_linktorsrc
issn:
  • 1932-6203
  • 19326203
url: Link


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titleTargeting human telomeric G-quadruplex DNA and inhibition of telomerase activity with [(dmb)2Ru(obip)Ru(dmb)2](4+)
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descriptionInhibition of telomerase by inducing/stabilizing G-quadruplex formation is a promising strategy to design new anticancer drugs. We synthesized and characterized a new dinuclear complex [(dmb).sub.2 Ru(obip)Ru(dmb).sub.2 ].sup.4+ (dmb = 4,4'-dimethyl-2,2'-bipyridine, obip = (2-(2-pyridyl)imidazo[4,5-f][1,10]phenanthroline) with high affinity for both antiparallel and mixed parallel / antiparallel G-quadruplex DNA. This complex can promote the formation and stabilize G-quadruplex DNA. Dialysis and TRAP experiments indicated that [(dmb).sub.2 Ru(obip)Ru(dmb).sub.2 ].sup.4+ acted as an excellent telomerase inhibitor due to its obvious selectivity for G-quadruplex DNA rather than double stranded DNA. In vitro co-culture experiments implied that [(dmb).sub.2 Ru(obip)Ru(dmb).sub.2 ].sup.4+ inhibited telomerase activity and hindered cancer cell proliferation without side effects to normal fibroblast cells. TUNEL assay indicated that inhibition of telomerase activity induced DNA cleavage further apoptosis in cancer cells. Therefore, Ru.sup.II complex represents an exciting opportunity for anticancer drug design by specifically targeting cancer cell G-quadruplexes DNA.
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titleTargeting human telomeric G-quadruplex DNA and inhibition of telomerase activity with [(dmb)2Ru(obip)Ru(dmb)2](4+)
description

Inhibition of telomerase by inducing/stabilizing G-quadruplex formation is a promising strategy to design new anticancer drugs. We synthesized and characterized a new dinuclear complex [(dmb)2Ru(obip)Ru(dmb)2](4+) (dmb = 4,4'-dimethyl-2,2'-bipyridine, obip = (2-(2-pyridyl)imidazo[4,5-f][1,10]phenanthroline) with high affinity for both antiparallel and mixed parallel / antiparallel G-quadruplex DNA. This complex can promote the formation and stabilize G-quadruplex DNA. Dialysis and TRAP experiments indicated that [(dmb)2Ru(obip)Ru(dmb)2](4+) acted as an excellent telomerase inhibitor due to its obvious selectivity for G-quadruplex DNA rather than double stranded DNA. In vitro co-culture experiments implied that [(dmb)2Ru(obip)Ru(dmb)2](4+) inhibited telomerase activity and hindered cancer cell proliferation without side effects to normal fibroblast cells. TUNEL assay indicated that inhibition of telomerase activity induced DNA cleavage further apoptosis in cancer cells. Therefore,...

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titleTargeting human telomeric G-quadruplex DNA and inhibition of telomerase activity with [(dmb)2Ru(obip)Ru(dmb)2](4+)
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Inhibition of telomerase by inducing/stabilizing G-quadruplex formation is a promising strategy to design new anticancer drugs. We synthesized and characterized a new dinuclear complex [(dmb)2Ru(obip)Ru(dmb)2](4+) (dmb = 4,4'-dimethyl-2,2'-bipyridine, obip = (2-(2-pyridyl)imidazo[4,5-f][1,10]phenanthroline) with high affinity for both antiparallel and mixed parallel / antiparallel G-quadruplex DNA. This complex can promote the formation and stabilize G-quadruplex DNA. Dialysis and TRAP experiments indicated that [(dmb)2Ru(obip)Ru(dmb)2](4+) acted as an excellent telomerase inhibitor due to its obvious selectivity for G-quadruplex DNA rather than double stranded DNA. In vitro co-culture experiments implied that [(dmb)2Ru(obip)Ru(dmb)2](4+) inhibited telomerase activity and hindered cancer cell proliferation without side effects to normal fibroblast cells. TUNEL assay indicated that inhibition of telomerase activity induced DNA cleavage further apoptosis in cancer cells. Therefore,...

pubPublic Library of Science (PLoS)
doi10.1371/journal.pone.0084419
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date2013-01-01