Nucleic acid aptamers have been proven to be a useful tool in many applications. Particularly, aptamers to epidermal growth factor receptor (EGFR) have been successfully used for the recognition of EGFR-expressing cells, the inhibition of EGFR-dependent pathways, and targeted drug delivery into EGFR-positive cells. Several aptamers are able to discriminate wild-type EGFR from its mutant form, EGFRvIII. Aptamers to EGFR have hairpin-like secondary structures with several possible folding variations. Here, an aptamer, previously selected to EGFRvIII, was chosen as a lead compound for extensive post-SELEX maturation. The aptamer was 1.5-fold truncated, the ends of the hairpin stem were appended with GC-pairs to increase thermal stability, and single pyrene modification was introduced into the aptamer to increase affinity to the target protein. Pyrene modification was selected from extensive computer docking studies of a library of thousands of chemicals to EGFR near the EGF-binding interface. The resulting aptamers bound extracellular domains of both variants of EGFR: EGFRwt and EGFRvIII with subnanomolar apparent dissociation constants. Compared with the initial aptamer, affinity to EGFRwt was increased up to 7.5-fold, whereas affinity to EGFRvIII was increased up to 4-fold.

中文翻译：

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对野生型 EGFR 和 EGFRvIII 具有高亲和力的芘修饰的 DNA 适体。

核酸适体已被证明是许多应用中的有用工具。特别是，表皮生长因子受体 (EGFR) 适配体已成功用于识别 EGFR 表达细胞、抑制 EGFR 依赖性通路以及将药物靶向递送至 EGFR 阳性细胞。几种适体能够将野生型 EGFR 与其突变形式 EGFRvIII 区分开来。EGFR 适体具有发夹状二级结构，具有多种可能的折叠变异。在这里，先前选择到 EGFRvIII 的适体被选为用于广泛的 SELEX 后成熟的先导化合物。适体被截短 1.5 倍，发夹茎的末端附加 GC 对以增加热稳定性，并在适体中引入单个芘修饰以增加对目标蛋白的亲和力。芘修饰是从对 EGF 结合界面附近的 EGFR 数千种化学物质库的广泛计算机对接研究中选择的。所得适体以亚纳摩尔表观解离常数结合 EGFR 两种变体的胞外结构域：EGFRwt 和 EGFRvIII。与初始适体相比，对 EGFRwt 的亲和力增加了 7.5 倍，而对 EGFRvIII 的亲和力增加了 4 倍。