SELEX and dynamic combinatorial chemistry interplay for the selection of conjugated RNA aptamers
SELEX and dynamic combinatorial chemistry interplay for the selection of conjugated RNA aptamers
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DOI：
10.1039/b610890c
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发表时间：
2006-01-01
影响因子：
3.2
通讯作者：
Rayner, Bernard
中科院分区：
文献类型：
--
作者：
Bugaut, Anthony;Toulme, Jean-Jacques;Rayner, Bernard
SELEX（用于通过指数富集的配体的系统进化）已被证明对于以高亲和力和特异性结合到广泛的分子靶标的DNA或RNA适体的分离非常强大。然而，核酸的适度化学功能对适体作为粘合剂和催化剂的多功能性造成了一些限制。为了进一步改善适体的性质，必须引入额外的化学多样性。化工模型设计。阳离子不是一个微不足道的任务。近年来，动态组合化学（DCC）被引入作为传统组合化学的替代。DCC采用平衡移动来实现分子的动态组合文库的分子进化。在此，我们描述了一种结合DCC和SELEX的原始方法，用于体外选择与化学上不同的小分子缀合的经修饰的适体。它的成功应用选择的小分子共轭RNA适体紧密结合的反式激活反应（TAR）元件的HIV-1。
SELEX (for Systematic Evolution of Ligands by Exponential enrichment) has proven to be extraordinarily powerful for the isolation of DNA or RNA aptamers that bind with high affinity and specificity to a wide range of molecular targets. However, the modest chemical functionality of nucleic acids poses some limits on the versatility of aptamers as binders and catalysts. To further improve the properties of aptamers, additional chemical diversity must be introduced. The design of chemical modi. cations is not a trivial task. Recently, dynamic combinatorial chemistry (DCC) has been introduced as an alternative to traditional combinatorial chemistry. DCC employs equilibrium shifting to effect molecular evolution of a dynamic combinatorial library of molecules. Herein, we describe an original process that combines DCC and SELEX for the in vitro selection of modified aptamers which are conjugated to chemically diverse small-molecules. Its successful application for the selection of small-molecule conjugated RNA aptamers that bind tightly to the transactivation-response (TAR) element of HIV-1 is presented.