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    • 5. 发明公开
    • CATIONIC OLIGONUCLEOTIDES, AUTOMATED METHODS FOR PREPARING SAME AND THEIR USES
    • 阳离子寡核苷酸,自动化的过程作为生产,用途
    • EP1973927A2
    • 2008-10-01
    • EP06847298.4
    • 2006-12-14
    • Centre National De La Recherche Scientifique-CNRSPolyPlus Transfection
    • BEHR, Jean-PaulKOTERA, MitsuharuPONS, BénédicteVOIRIN, EmilieREMY, Jean-Serge
    • C07H21/00
    • C07F9/22A61K47/59A61K48/0041C07H21/00C12N15/88
    • The invention relates to oligonucleotide-oligocation molecules AiBjH that can be synthetized via automated phosphoramidite chemistry having oligonucleotides moieties Ai and oligocations moieties Bj, wherein . Ai is an i-mer oligonucleotide residue, with i = 5 to 50, where nucleotide A is an oligomer with naturally or non naturally occurring nucleobases and/or pentafuranosyl groups and/or native phosphodiester bonds, for example selected from the group comprising deoxyribo, ribo, locked (LNA) nucleotides as well as their chemical modifications or substitutions such as phosphorothioate, 2'-fluoro, 2'-O-alkyl, or a marker group such as a fluorescent agent, . Bj is a j-mer organic oligocation moiety, with j = 1 to 50, where B is selected from the group comprising • - HPO3-R1 -(X-R2n)n1-X-R3-O-, where R1, R2n and R3, identical or different, are lower alkylene, X is NH or NC(NH2)2, n varies from 1 to 5 and n1 = 2 to 20, • - HPO3-R4-CH(R5X1)-R6-O-, where R4 is lower alkylene, R5 and R6, identical or different, are lower alkylene and X1 is putrescine, spermidine or spermine residue, • - HPO3-R7-(aa)n2-R8-O-, where R7 is lower alkylene and R8 is lower alkylene, serine, a natural aminoalcohol, (aa)n2 is a peptide containing natural aminoacids with cationic side chains, such as Arginine, Lysine, Ornithine, - Histidine, Diaminopropionic acid and n2= 2 to 20.
    • 本发明涉及的寡核苷酸 - 寡聚阳离子分子AiBjH确实可以经由具有寡核苷酸部分A i和寡阳离子部分BJ自动化亚磷酰胺化学synthetized,worin•艾是i聚体寡核苷酸残基,其中i = 5〜50,其中核苷酸A是低聚 与选自天然或非天然存在的核碱基和/或pentafuranosyl基团和/或天然磷酸二酯键,例如包括脱氧核糖,核糖,锁定(LNA)核苷酸以及其化学修饰或取代:例如硫代磷酸酯,2'- 氟,2'-O-烷基或标记基团:如荧光剂,•BJ是第j聚体有机寡聚阳离子部分,其中j = 1至50,其中B选自包括以下的组•-HPO3-R1选择 - (X-R 2n)后N1-X-R3-O-,其中R 1,R 2 N和R 3,相同或不同,是低级亚烷基,X是NH或NC(NH 2)2,N从1变化至5并且n1 = 2 至20,•-HPO3-R4-CH(R5X1)-R 6 -O-,其中R 4是低级 亚烷基,R5和R6,相同或不同,是低级亚烷基和X 1为腐胺,亚精胺或精胺残基,•-HPO3-R7(AA)N2-R8-O-,其中R 7是低级亚烷基和R 8是低级亚烷基, 丝氨酸,天然氨基醇(AA)n2是含有具有阳离子侧链的,:如精氨酸,赖氨酸,鸟氨酸,组氨酸,二氨基丙酸和n2 = 2到20的自然氨基酸的肽