INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM);CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE;UNIVERSITÉ DE BORDEAUX
发明人:
BARTHELEMY, Philippe,GISSOT, Arnaud,VIALET, Brune
申请号：
EPEP2019/082915
公开号：
WO2020/109470A1
申请日:
2019.11.28
申请国别(地区):
EP
年份:
2020
代理人:
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 (tp G4). 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 at the 5' or 3' end 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 at the 5' or 3' end 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.La présente invention concerne des oligonucléotides formant des G-quadruplexes tétramoléculaires parallèles. Si les G-quadruplexes sont d'importance primordiale en biologie, leur utilisation est gênée par la propension de molécules d'ADN sujettes à la formation de G4, en particulier de molécules d'ADN sujettes à la formation de G4 de taille longue, à adopter de nombreuses conformations topologiques G4 différentes ou d'autres repliements alternatifs. Par introduction d'une modification lipidique à l'extrémité de l'oligonucléotide, les inventeurs ont réussi à obtenir des G-quadruplexes tétramoléculaires parallèles longs (tpG4). La présente invention concerne ainsi un oligonucléotide modifi
