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pubmed-article:15760901pubmed:abstractTextTriplex-forming oligonucleotides (TFOs), as DNA-binding molecules that recognize specific sequences, offer unique potential for the understanding of processes occurring on DNA and associated functions. They are also powerful DNA recognition elements for the positioning of ubiquitous molecules acting on DNA, such as anticancer drugs. A prerequisite for further development of DNA code-reading molecules including TFOs is their ability to form a complex in a cellular context: their binding affinities must be comparable to those of DNA-associated proteins. To reach this goal, chemically modified TFOs must be developed. In this work, we present triplex-forming properties (kinetics and thermodynamics) and cellular activity of G-containing locked nucleic acid-modified TFOs (TFO/LNAs). In conditions simulating physiological ones, these TFO/LNAs strongly enhanced triplex stability compared with the non-modified TFO or with the pyrimidine TFO/LNA directed against the same oligopyrimidine.oligopurine sequence, mainly by decreasing the dissociation rate constant and conferring an entropic gain. We provide evidence of their biological activity by a triplex-based mechanism, in vitro and in a cellular context, under conditions in which the parent phosphodiester oligonucleotide did not exhibit any inhibitory effect.lld:pubmed
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pubmed-article:15760901pubmed:pagination20076-85lld:pubmed
pubmed-article:15760901pubmed:dateRevised2007-11-15lld:pubmed
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pubmed-article:15760901pubmed:year2005lld:pubmed
pubmed-article:15760901pubmed:articleTitleExploring cellular activity of locked nucleic acid-modified triplex-forming oligonucleotides and defining its molecular basis.lld:pubmed
pubmed-article:15760901pubmed:affiliationLaboratoire de Biophysique, Museum National d'Histoire Naturelle USM 503, CNRS UMR 5153, INSERM U 565, Paris, France.lld:pubmed
pubmed-article:15760901pubmed:publicationTypeJournal Articlelld:pubmed
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pubmed-article:15760901pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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