Bugaut Anthony, Toulmé Jean-Jacques, Rayner Bernard
INSERM U386, 146 rue Leo Saignat, 33076 BORDEAUX Cedex, France.
Org Biomol Chem. 2006 Nov 21;4(22):4082-8. doi: 10.1039/b610890c.
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 modifications 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.
指数富集配体系统进化技术（SELEX）已被证明在分离能与多种分子靶标高亲和力和特异性结合的DNA或RNA适配体方面具有非凡的强大功能。然而，核酸适度的化学功能对适配体作为结合剂和催化剂的通用性造成了一些限制。为了进一步改善适配体的性质，必须引入额外的化学多样性。化学修饰的设计并非易事。最近，动态组合化学（DCC）已作为传统组合化学的替代方法被引入。DCC利用平衡移动来实现分子动态组合库的分子进化。在此，我们描述了一种将DCC和SELEX相结合的原始方法，用于体外筛选与化学性质多样的小分子共轭的修饰适配体。展示了其在筛选与HIV-1反式激活应答（TAR）元件紧密结合的小分子共轭RNA适配体方面的成功应用。
