Conformational Switching of a Foldamer in a Multicomponent System by pH-Filtered Selection between Competing Noncovalent Interactions.
Conformational Switching of a Foldamer in a Multicomponent System by pH-Filtered Selection between Competing Noncovalent Interactions.
复制标题
DOI：
10.1021/jacs.5b03284
复制
发表时间：
2015-05-27
影响因子：
15
通讯作者：
Clayden J
中科院分区：
文献类型：
--
作者：
Brioche J;Pike SJ;Tshepelevitsh S;Leito I;Morris GA;Webb SJ;Clayden J
生物分子系统能够通过可逆的、选择性的、非共价的分子间相互作用来响应它们的化学环境。通常，这些相互作用诱导构象变化，启动信号级联，允许生化途径的调节。在这项工作中，我们描述了一个人工分子系统，模仿这种能力，将选择性非共价相互作用转化为可逆的构象变化。携带基本结合位点的非手性螺旋折叠体选择性地与一组手性配体中酸性最强的成员相互作用。作为这种非共价相互作用的结果，在折叠体中诱导了一种全球绝对螺旋感偏好，可以通过13C核磁共振检测到。在配体混合物中加入碱或酸，竞争性地调节它们与结合位点的相互作用，并可逆地在其左、右手构象之间切换折叠体链。因此，折叠体-配体混合物表现为具有涌现特性的仿生化学系统，作为“质子计数”分子装置，能够对其环境提供可调的、依赖ph的构象响应。
Biomolecular systems are able to respond to their chemical environment through reversible, selective, noncovalent intermolecular interactions. Typically, these interactions induce conformational changes that initiate a signaling cascade, allowing the regulation of biochemical pathways. In this work, we describe an artificial molecular system that mimics this ability to translate selective noncovalent interactions into reversible conformational changes. An achiral but helical foldamer carrying a basic binding site interacts selectively with the most acidic member of a suite of chiral ligands. As a consequence of this noncovalent interaction, a global absolute screw sense preference, detectable by 13C NMR, is induced in the foldamer. Addition of base, or acid, to the mixture of ligands competitively modulates their interaction with the binding site, and reversibly switches the foldamer chain between its left and right-handed conformations. As a result, the foldamer–ligand mixture behaves as a biomimetic chemical system with emergent properties, functioning as a “proton-counting” molecular device capable of providing a tunable, pH-dependent conformational response to its environment.