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1. WO2020109470 - TETRAMOLECULAR PARALLEL G-QUADRUPLEX-FORMING HYDROPHOBICALLY MODIFIED OLIGONUCLEOTIDES

Publication Number WO/2020/109470
Publication Date 04.06.2020
International Application No. PCT/EP2019/082915
International Filing Date 28.11.2019
IPC
C07H 21/00 2006.01
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
21Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
A61K 31/712 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
70Carbohydrates; Sugars; Derivatives thereof
7088Compounds having three or more nucleosides or nucleotides
712Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
C07H 21/04 2006.01
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
21Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
04with deoxyribosyl as saccharide radical
CPC
C07H 21/00
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
21Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
C07H 21/04
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
21Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
04with deoxyribosyl as saccharide radical
Applicants
  • INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM) [FR]/[FR]
  • CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE [FR]/[FR]
  • UNIVERSITÉ DE BORDEAUX [FR]/[FR]
Inventors
  • BARTHELEMY, Philippe
  • GISSOT, Arnaud
  • VIALET, Brune
Agents
  • BLOT, Philippe
  • DOMENEGO, Bertrand
  • HOLTZ, Béatrice
  • HABASQUE, Etienne
  • COLOMBIE, Damien
  • NEYRET, Daniel
Priority Data
18306595.230.11.2018EP
Publication Language English (EN)
Filing Language English (EN)
Designated States
Title
(EN) TETRAMOLECULAR PARALLEL G-QUADRUPLEX-FORMING HYDROPHOBICALLY MODIFIED OLIGONUCLEOTIDES
(FR) OLIGONUCLÉOTIDES A MODIFICATION HYDROPHOBE FORMANT DES G-QUADRUPLEXES TÉTRAMOLÉCULAIRES PARALLÈLES
Abstract
(EN)
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.
(FR)
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 modifié par substitution au niveau de l'extrémité 5' ou 3' par une fraction lipidique, ledit oligonucléotide comprenant une séquence d'acide nucléique d'au moins 10 nucléotides, ladite séquence d'acide nucléique comprenant une série d'au moins 4 résidus de guanine consécutifs situés à l'extrémité 5' ou 3' de ladite séquence. L'invention concerne en outre un G-quadruplexe tétramoléculaire parallèle comprenant 4 oligonucléotides modifiés identiques tels que définis ci-dessus, chacun des 4 résidus de guanine consécutifs inclus à l'extrémité 5' ou 3' de la séquence d'acide nucléique de chaque oligonucléotide formant respectivement des G-quartets avec les résidus de guanine correspondants des 3 autres oligonucléotides, lesdits G-quartets étant stabilisés par disposition π-π et liaison hydrogène de Hoogsteen.
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