High-Affinity Nucleic-Acid-Based Receptors for Steroids,ACS Chemical Biology

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High-Affinity Nucleic-Acid-Based Receptors for Steroids
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2017-11-22 00:00:00 , DOI: 10.1021/acschembio.7b00634
Kyung-Ae Yang , Hyosun Chun ₁ , Yameng Zhang , Stevan Pecic , Nako Nakatsuka _{2,

3} , Anne M. Andrews _{2,

3,

4} , Tilla S. Worgall , Milan N. Stojanovic

Affiliation

Artificial receptors for hydrophobic molecules usually have moderate affinities and limited selectivities. We describe three new classes of high affinity hydrophobic receptors for nonaromatic steroids based on deoxyribonucleotides, obtained through five high stringency selections coupled with tailored counter-selections. The isolation of multiple classes of high affinity steroid receptors demonstrates the surprising breadth of moderately sized hydrophobic binding motifs (<40 nucleotides) available to natural nucleic acids. Studies of interactions with analogs indicate that two classes, four-way junctions and 4XG_N motifs, comprise receptors with shapes that prevent binding of specific steroid conjugates used in counter-selections. Furthermore, they strongly prefer nonhydroxylated steroid cores, which is typical for hydrophobic receptors. The third new class accommodates hydroxyl groups in high-affinity, high-selectivity binding pockets, thus reversing the preferences of the first two classes. The high-affinity binding of aptamers to targets efficiently inhibits double-helix formation in the presence of the complementary oligonucleotides. The high affinity of some of these receptors and tailored elimination of binding through counter-selections ensures that these new aptamers will enable clinical chemistry applications.

中文翻译：

类固醇的高亲和力基于核酸的受体

疏水分子的人工受体通常具有中等亲和力和有限的选择性。我们描述基于脱氧核糖核苷酸的非芳香类固醇的三类新的高亲和力疏水受体，通过五个高严格选择与量身定制的反选择获得。多种类型的高亲和力类固醇受体的分离证明了天然核酸可利用的中等大小的疏水性结合基序（<40个核苷酸）的令人惊讶的广度。与类似物相互作用的研究表明，有两类，四通接头和4XG _N基序包含具有防止在反选择中使用的特定类固醇结合物结合的形状的受体。此外，他们强烈希望使用非羟基化的类固醇核心，这是疏水性受体的典型特征。第三类新分子在高亲和力，高选择性结合口袋中容纳了羟基，从而颠倒了前两类的偏好。在互补寡核苷酸的存在下，适体与靶标的高亲和力结合有效地抑制了双螺旋的形成。这些受体中的某些具有高亲和力，并通过反选择有针对性地消除了结合，从而确保了这些新的适体将可用于临床化学应用。

更新日期：2017-11-23

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