Exploring the Limits of Bivalency by DNA-Based Spatial Screening
Exploring the Limits of Bivalency by DNA-Based Spatial Screening
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DOI：
10.1002/anie.201810996
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发表时间：
2019-01-14
影响因子：
16.6
通讯作者：
Seitz, Oliver
中科院分区：
文献类型：
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作者：
Dubel, Natali;Liese, Susanne;Seitz, Oliver
当单价受体-配体相互作用较弱时，多价性可促进复合物形成。然而，两个多价结合配偶体的增强结合应该是可避免的，例如当二价受体应该利用多分子相互作用来交联结合配偶体时。我们在此报告的第一个系统的研究，以评估的标准，决定是否二价系统从事二价增强的相互作用或交联。我们使用DNA指导的自组装将葫芦[7]脲-金刚烷主客体系统排列在70-360埃的距离。测量和统计力学分析表明，亲和力增益受1）识别模块之间的距离，2）支架柔性，以及重要的是，3）单价相互作用的强度控制。我们发现，二价效应可以延伸到150埃以上，并讨论如何，相反，弱单价相互作用降低交联的浓度阈值。研究结果是感兴趣的抑制剂设计。
Multivalency can facilitate complex formation when monovalent receptor-ligand interactions are weak. However, enhanced binding of two multivalent binding partners should be avoidable, for example when bivalent receptors ought to utilize multimolecular interactions to cross-link binding partners. We herein report the first systematic study to assess the criteria deciding whether a bivalent system engages in bivalency-enhanced interactions or cross-linking. We used DNA-instructed self-assembly to arrange the cucurbit[7]uril-adamantane host-guest system in 70-360 angstrom distance. Measurements and statistical mechanics analyses revealed that the affinity gain is controlled by 1) the distance between recognition modules, 2) the scaffold flexibility, and, importantly, 3) the strength of the monovalent interaction. We show that the bivalency effect can extend beyond 150 angstrom and discuss how, on the contrary, weak monovalent interactions reduce the concentration threshold for cross-linking. The findings are of interest for inhibitor design.