Evidence for higher-order structure formation by the c-myb 18-mer phosphorothioate antisense (codons 2-7) oligodeoxynucleotide: potential relationship to antisense c-myb inhibition.
Evidence for higher-order structure formation by the c-myb 18-mer phosphorothioate antisense (codons 2-7) oligodeoxynucleotide: potential relationship to antisense c-myb inhibition.
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c-myb 18 聚体硫代磷酸酯反义（密码子 2-7）寡脱氧核苷酸形成高阶结构的证据：与反义 c-myb 抑制的潜在关系。
DOI：
10.1089/108729001750171317
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Stein,CA
中科院分区：
文献类型：
--
作者：
Vilenchik,M;Benimetsky,L;Kolbanovsky,A;Miller,P;Stein,CA
我们已经证明了一个18聚体的硫代磷酸反义c-myboligodeoxyribonucleotide具有活性， 白血病异种移植模型的治疗。尽管通过常规采用的技术如PAGE和硫酸二甲酯（DMS）保护不能观察到，但这种高级结构的形成 通过几种技术揭示了这种寡核苷酸。这些包括毛细管凝胶电泳（CGE），它证明了分子的存在与大大增加的保留时间相比， 与单体;磁性圆二色性光谱，其显示了在290 nm处的带，这是反平行四链体的特征;和荧光能量转移测量。最后， 用5 ′-荧光素基团合成18-mer硫代磷酸酯寡核苷酸。类似于分子信标模型，当在溶液中与四链体形成结合时， 含有3 '-Dabcyl部分的低聚物。7-脱氮鸟苷通过消除Hoogsteen碱基对相互作用抑制四链体的形成。野生型和7-脱氮鸟苷取代的反义 c-myboligomers差异下调表达的c-myb原癌基因在K562和HL 60细胞，与野生型寡聚体是最不活跃。因此，18-mer c-myb分子可以形成高度复杂的结构，其在溶液中的分析不能仅限于平板凝胶电泳结果的检查。
We have demonstrated the formation of higher-order structures (presumably tetraplexes) by an 18-mer phosphorothioate antisense c-myboligodeoxyribonucleotide that has been shown to have activity in the treatment of leukemia xenograft models. Although not observable by conventionally employed techniques, such as PAGE and dimethyl sulfate (DMS) protection, the formation of such higher-order structures by this oligonucleotide was revealed by several techniques. These included capillary gel electrophoresis (CGE), which demonstrated the presence of molecules with greatly increased retention time compared with the monomer; magnetic circular dichroism spectroscopy, which demonstrated a band at 290 nm, a characteristic of antiparallel tetraplexes; and fluorescence energy transfer measurements. For the last, the 18-mer phosphorothioate oligonucleotide was synthesized with a 5'-fluorescein group. Similar to the molecular beacon model, its fluorescence was quenched when combined in solution with tetraplex-forming oligomers that contained a 3'-Dabcyl moiety. 7-Deazaguanosine inhibits the formation of tetraplexes by eliminated Hoogsteen base pair interactions. The wild-type and 7-deazaguanosine-substituted antisense c-myboligomers differentially downregulated the expression of the c-mybproto-oncogene in K562 and HL60 cells, with the wild-type oligomer being the least active. The 18-mer c-mybmolecule can, therefore, form highly complex structures, whose analysis in solution cannot be limited to examination of slab gel electrophoresis results alone.
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寡核苷酸和类似物：实用方法
DOI：
--
发表时间：
1991
期刊：
影响因子：
--
作者：
F. Eckstein
通讯作者：
F. Eckstein
DOI：
10.1073/pnas.89.18.8832
发表时间：
1992-09-15
影响因子：
11.1
作者：
JIN, RZ;GAFFNEY, BL;BRESLAUER, KJ
通讯作者：
BRESLAUER, KJ
影响因子：
2.9
作者：
HARDIN, CC;HENDERSON, E;PROSSER, JK
通讯作者：
PROSSER, JK
使用 c-myb 反义寡脱氧核苷酸在 scid 小鼠模型中体内治疗人白血病。
DOI：
10.1073/pnas.89.24.11823
发表时间：
1992
影响因子：
11.1
作者：
Ratajczak,MZ;Kant,JA;Luger,SM;Hijiya,N;Zhang,J;Zon,G;Gewirtz,AM
通讯作者：
Gewirtz,AM
影响因子：
2.9
作者：
Marotta, SP;Tamburri, PA;Sheardy, RD
通讯作者：
Sheardy, RD