Binding Studies on a Library of Induced-Fit Synthetic Carbohydrate Receptors with Mannoside Selectivity
Binding Studies on a Library of Induced-Fit Synthetic Carbohydrate Receptors with Mannoside Selectivity
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DOI：
10.1002/chem.201803317
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发表时间：
2018-09-18
影响因子：
4.3
通讯作者：
Braunschweig, Adam B.
中科院分区：
文献类型：
--
作者：
Palanichamy, Kalanidhi;Bravo, M. Fernando;Braunschweig, Adam B.
合成碳水化合物受体可以作为疾病检测、药物输送甚至治疗的试剂，然而，它们很少用于这些应用，因为它们结合得很弱，而且偏爱细胞表面不常见的全赤道糖苷。本文报道了8种受体与5种不同的辛氧基吡喃糖苷在298K时在Cd_2Cl2中的结合，其结合亲和力约为10(1)-10(4)m(-1)。虽然受体是混杂的，但1对-Man的选择性为103：1-Man：-Gal，受体2-4和6对-Man有选择性，5对-Gal有选择性，10对-Glc有选择性(Man=甘露糖；Gal=半乳糖，Glc=葡萄糖)。用各种一维和二维核磁共振和计算技术确定了热力学结合参数(H-O和S-O)和主客体络合物的结构，揭示了二聚体受体10与MAN结合的热焓增加，但熵惩罚大于1。第一性原理模拟表明，10-MAN形成包含型络合物，其中糖通过氢键和C-H相互作用与10的两个单体亚基结合。与天然糖结合蛋白一样，这些受体通过参与多价和协同作用与吡喃糖苷结合，这些研究提出了一种新的仿生合成碳水化合物受体的方法，其中构象灵活性和混杂被结合到设计中。
Synthetic carbohydrate receptors could serve as agents for disease detection, drug delivery, or even therapeutics, however, they are rarely used for these applications because they bind weakly and with a preference towards the all-equatorial glucosides that are not prevalent on the cell surface. Herein the binding of 8 receptors with 5 distinct octyloxy pyranosides, which was measured by mass spectrometry and by (HNMR)-H-1 titrations in CD2Cl2 at 298K, is reported, providing binding affinities that vary from approximate to 10(1)-10(4)m(-1). Although the receptors are promiscuous, 1 shows selectivity for -Man at a ratio of 103:1 -Man:-Gal, receptors 2-4 and 6 have preference for -Man, 5 is selective for -Gal, and 10 prefers -Glc (Man=mannose; Gal=galactose, Glc=glucose). A variety of 1D and 2D NMR, and computational techniques were used to determine the thermodynamic binding parameters (H-o and S-o) and the structure of the host-guest complex, revealing that dimeric receptor 10 binds -Man with increased enthalpy, but a larger entropic penalty than 1. The first-principles modelling suggests that 10-Man forms an inclusion-type complex where the glycan engages both monomeric subunits of 10 through H-bonding and C-H interactions. Like natural glycan-binding proteins, these receptors bind pyranosides by accessing multivalent and cooperative interactions, and these studies suggest a new approach towards biomimetic synthetic carbohydrate receptors, where conformational flexibility and promiscuity are incorporated into design.