Stabilization of DNA Triple Helices Using Conjugates of Oligonucleotides and Synthetic Ligands |
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Authors: | Sinyakov A N Ryabinin V A Grimm G N Boutorine A S |
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Institution: | (1) Institute of Molecular Biology, State Research Center VECTOR, Kol tsovo, Novosibirsk Region, 630559, Russia;(2) Laboratoire de Biophysique, Muséum National d Histoire Naturelle, (INSERM U201–CNRS UMR 8646), 75231 Paris 05, France |
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Abstract: | The possibility is discussed of stabilizing a DNA triple helix by covalent conjugation to the third strand (through its terminal phosphate) of ligands that have affinity to double and triple helices. Two types of stabilizers are considered: minor groove binders based on oligopyrroles, and triplex-specific intercalators. As a target, a synthetic 29-mer duplex containing a natural polypurine sequence of the human immunodeficiency provirus was employed. The stabilization with minor groove binders requires several conditions to be respected: a sufficiently long linker capable of reaching the minor groove from the major groove, a specific double-stranded structure of the oligopyrrole fragment, and its in-phase fitness to the target sequence. The best stabilizers of a triplex were novel conjugates in which two parallel molecules containing six pyrrole units each are linked to the same 5"-phosphate of a 16-mer triplex-forming oligonucleotide. The stabilizing properties of these derivatives were comparable to those of benzoindoloquinoline (BIQ) intercalators attached to the terminal phosphate of triple-helix forming oligonucleotides. |
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Keywords: | oligodeoxyribonucleotide minor groove binder intercalator terminal phosphate activation conjugate DNA triple helix stabilization melting temperature |
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