申请人:——
公开号:US20040142946A1
公开(公告)日:2004-07-22
The present invention relates to modified nucleotides and nucleosides and reagents to produce these. The modified nucleotides and nucleotides are assembled to larger oligonucleotides and oligonucleosides, which, for example, may be used for diagnostics of polymorphisms and for antisense therapy of various conditions. The oligonucleotides and oligonucleosides described in the invention have very good endonuclease resistance without compromising the RNA cleavage properties of RNase H wherein combinations of modifications with Y, Z, R or B are claimed: X=O or S, NH or NCH
3
, CH
2
Or CH(CH
3
), Y=O, S, or NH or NCH
3
, CH
2
or CH(CH
3
); Z=O, S, or NH or NCH
3
, CH
2
or CH(CH
3
); R=O or S, or NH or NCH
3
, CH
2
or CH(CH
3
); B=A, C, G, T; 5-F/cl/BrU or —C, 6-thioguanine, 7-deazaguanine; &agr;- or &bgr;-
D
- (or
L
)ribo, xylo, arabino or lyxo configuration.
本发明涉及修饰的核苷酸和核苷以及生产这些核苷酸和核苷的试剂。经修饰的核苷酸和核苷酸可组装成更大的寡核苷酸和寡核苷酸,例如可用于多态性诊断和各种疾病的反义治疗。本发明所述的寡核苷酸和寡核苷酸具有很好的抗核酸内切酶性,同时不影响 RNase H 的 RNA 裂解特性,其中与 Y、Z、R 或 B 的修饰组合是所要求的:X=O or S, NH or NCH
3
, CH
2
或 CH(CH
3
),Y 等于;O、S 或 NH 或 NCH
3
,CH
2
或 CH(CH
3
); Z=O, S, or NH or NCH
3
,CH
2
或 CH(CH
3
); R=O 或 S,或 NH 或 NCH
3
,CH
2
或 CH(CH
3
); B=A, C, G, T; 5-F/cl/BrU or -C, 6-thioguanine, 7-deazaguanine; &agr;- or &bgr;-
D
- 或
L
)ribo、xylo、阿拉伯或 lyxo 构型。