Targeted inhibition of Snail family zinc finger transcription factors by oligonucleotide-Co(III) Schiff base conjugate
Targeted inhibition of Snail family zinc finger transcription factors by oligonucleotide-Co(III) Schiff base conjugate
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DOI：
10.1073/pnas.0906423106
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发表时间：
2009-08-18
影响因子：
11.1
通讯作者：
Meade, Thomas J.
中科院分区：
文献类型：
--
作者：
Harney, Allison S.;Lee, Jiyoun;Meade, Thomas J.
一种以抑制锌指转录因子为靶点的过渡金属络合物已被合成，并在非洲爪哇进行了测试。设计了一种用17bP DNA序列修饰的Co(III)Schiff碱配合物，以选择性地抑制Snail家族转录因子。寡核苷酸连接的Co(III)络合物阻止Slug、Snail和SIP1与它们的DNA靶标结合，而其他转录因子仍然能够与它们的靶DNA相互作用。将寡核苷酸连接到Co(III)络合物上比未结合的络合物提高了150倍的特异性。研究表明，无论是寡聚，还是钴(III)席夫碱络合物本身，都不足以在偶联络合物介导的抑制浓度下灭活段塞。Slug、Snail和SIP1参与了发育和癌症上皮向间充质转化的调控。一种旨在使其转录活性失活的复合体可能被证明是一种有价值的实验工具和癌症治疗方法。
A transition metal complex targeted for the inhibition of a subset of zinc finger transcription factors has been synthesized and tested in Xenopus laevis. A Co(III) Schiff base complex modified with a 17-bp DNA sequence is designed to selectively inhibit Snail family transcription factors. The oligonucleotide-conjugated Co(III) complex prevents Slug, Snail, and Sip1 from binding their DNA targets whereas other transcription factors are still able to interact with their target DNA. The attachment of the oligonucleotide to the Co( III) complex increases specificity 150-fold over the unconjugated complex. Studies demonstrate that neither the oligo, or the Co(III) Schiff base complex alone, are sufficient for inactivation of Slug at concentrations that the conjugated complex mediates inhibition. Slug, Snail, and Sip1 have been implicated in the regulation of epithelial-to-mesenchymal transition in development and cancer. A complex targeted to inactivate their transcriptional activity could prove valuable as an experimental tool and a cancer therapeutic.