Regiochemical Effects on the Carbohydrate Binding and Selectivity of Flexible Synthetic Carbohydrate Receptors with Indole and Quinoline Heterocyclic Groups.
Regiochemical Effects on the Carbohydrate Binding and Selectivity of Flexible Synthetic Carbohydrate Receptors with Indole and Quinoline Heterocyclic Groups.
复制标题
区域化学效应对具有吲哚和喹啉杂环基的柔性合成碳水化合物受体的碳水化合物结合和选择性。
DOI：
10.1002/ejoc.202100763
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发表时间：
2021-10-07
影响因子：
2.8
通讯作者：
Braunschweig, Adam B.
中科院分区：
文献类型：
--
作者：
Thakur, Khushabu;Shlain, Milan A.;Marianski, Mateusz;Braunschweig, Adam B.
关键词：
结合细胞表面碳水化合物的合成碳水化合物受体（SCR）可用于疾病检测、药物递送和治疗，或用于复杂碳水化合物的位点选择性修饰，但由于与结合亲和力和底物选择性相关的剩余挑战，它们的潜力尚未实现。我们最近报道了一系列基于联芳基核和四个侧链杂环基团的柔性SCR，这些杂环基团通过非共价相互作用选择性地结合聚糖。在这里，我们通过扩大我们的库以包括一系列吲哚和喹啉杂环，继续探索杂环对底物选择性的作用，这些杂环在与联芳基核心的连接区域化学上有所不同。这些SCR的一系列生物相关的碳水化合物的结合进行了研究，通过1H NMR滴定在CD2Cl2和密度泛函理论计算。我们发现SCR030、SCR034和SCR037是选择性的，SCR031、SCR032和SCR039是强结合剂，SCR033、SCR035、SCR036和SCR038是混杂的，结合较弱。计算分析揭示了C−H π和H键相互作用在定义这些新受体的结合特性中的重要性。通过将这些数据与我们以前对这类柔性SCR的研究中获得的数据相结合，我们开发了一系列设计规则，这些规则解释了这类所有SCR的结合，并预测了未来尚未想象到的四足SCR的结合。本文研究了糖受体与一系列糖类化合物结合的区域化学和杂环基团的结构对糖受体结合的影响。这导致了预期结构修饰如何影响SCR结合亲和力和特异性的设计规则。
Synthetic carbohydrate receptors (SCRs) that bind cell-surface carbohydrates could be used for disease detection, drug-delivery, and therapeutics, or for the site-selective modification of complex carbohydrates but their potential has not been realized because of remaining challenges associated with binding affinity and substrate selectivity. We have reported recently a series of flexible SCRs based upon a biaryl core with four pendant heterocyclic groups that bind glycans selectively through noncovalent interactions. Here we continue to explore the role of heterocycles on substrate selectivity by expanding our library to include a series of indole and quinoline heterocycles that vary in their regiochemistry of attachment to the biaryl core. The binding of these SCRs to a series of biologically-relevant carbohydrates was studied by 1H NMR titrations in CD2Cl2 and density-functional theory calculations. We find SCR030, SCR034 and SCR037 are selective, SCR031, SCR032, and SCR039 are strong binders, and SCR033, SCR035, SCR036, and SCR038 are promiscuous and bind weakly. Computational analysis reveals the importance of C−H⋯π and H-bonding interactions in defining the binding properties of these new receptors. By combining these data with those obtained from our previous studies on this class of flexible SCRs, we develop a series of design rules that account for the binding of all SCRs of this class and anticipate the binding of future, not-yet imagined tetrapodal SCRs. The effects of regiochemistry of attachment and structure of heterocyclic groups on the binding between synthetic carbohydrate receptors (SCRs) and a series of carbohydrates was studied. This resulted in design rules that anticipate how structural modifications affect SCR binding affinity and specificity.
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通讯作者：
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