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    TETRAMOLECULAR PARALLEL G-QUADRUPLEX-FORMING HYDROPHOBICALLY MODIFIED OLIGONUCLEOTIDES
    3.
    发明申请
    TETRAMOLECULAR PARALLEL G-QUADRUPLEX-FORMING HYDROPHOBICALLY MODIFIED OLIGONUCLEOTIDES 审中-公开

    公开(公告)号：US20200181607A1

    公开(公告)日：2020-06-11

    申请号：US16617631

    申请日：2018-06-01

    申请人： INSERM (Institute National de la Santé et de la Recherche Médicale) ,  Centre National de la Recherche Scientifique ,  Université de Bordeaux

    发明人： Philippe BARTHELEMY ,  Arnaud GISSOT ,  Brune VIALET

    IPC分类号： C12N15/11

    摘要： The present invention relates to tetramolecular parallel G-quadruplex-forming oligonucleotides. If G-quadruplexes are of prime importance in biology, their use is hampered by the propensity of G4-prone DNA molecules, in particular G4-prone DNA molecules of long size, to adopt many different G4 topological conformations or other alternative foldings. By introducing a lipid modification at the end of the oligonucleotide, the inventors succeeded in obtaining long tetramolecular parallel G-quadruplexes (tpG4). The present invention thus concerns an oligonucleotide modified by substitution at the 5′ or the 3′ end by a lipid moiety, wherein said oligonucleotide comprises a nucleic acid sequence of at least 10 nucleotides, said nucleic acid sequence including a series of at least 4 consecutive guanine residues located in the middle of said sequence. A tetramolecular parallel G-quadruplex comprising 4 identical modified oligonucleotides as defined above, wherein each of the 4 consecutive guanine residues included in the middle of the nucleic acid sequence of each oligonucleotide respectively form G-quartets with the corresponding guanine residues of the other 3 oligonucleotides, said G-quartets being stabilized by π-π staking and Hoogsteen hydrogen bonding, is also contemplated. The modified oligonucleotides have preferably the general formula (I) or (II), wherein the oligonucleotides are modified by substitution at the 5′ or the 3′ end by a lipid moiety, and said oligonucleotides comprise a nucleic acid sequence of at least 10 nucleotides, said nucleic acid sequence including a series of at least 4 consecutive guanine residues located in the middle of said sequence.