High fidelity kinetic self-sorting in multi-component systems based on guests with multiple binding epitopes
High fidelity kinetic self-sorting in multi-component systems based on guests with multiple binding epitopes
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DOI：
10.1021/ja063390j
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发表时间：
2006-11-01
影响因子：
15
通讯作者：
Isaacs, Lyle
中科院分区：
文献类型：
--
作者：
Mukhopadhyay, Pritam;Zavalij, Peter Y.;Isaacs, Lyle
自然系统的分子识别平台通常具有多个结合表位，每个表位都有编程的功能后果。我们报道了一个由CB[6]、CB[7]以及客体环己二胺(1)和金刚烷基胺(2)组成的体系的动态行为，我们称之为双面客体，因为它包含两个不同的结合表位。我们发现，双面客体的存在--就像在体内观察到的蛋白质靶向一样--决定了系统走向平衡的动力学路径。通过实验和模拟相结合的方法，探讨了双面客体结构、阳离子浓度、阳离子同一性、个体速率常数和平衡常数对体系行为的影响。对该体系的解构导致发现了一个异常的主客体复合体(CB[6]中心点1)，其解离速率常数k(Out)=8.5x10(-10)S(-1)比广泛使用的亲和素生物素亲和对慢近100倍。这一结果，结合对先前发现异常紧密结合事件(K-a>；=10(12)M-1)的系统的分析，突出了追求超分子化学的系统方法的内在潜力。
The molecular recognition platforms of natural systems often possess multiple binding epitopes, each of which has programmed functional consequences. We report the dynamic behavior of a system comprising CB[6], CB[7], and guests cyclohexanediammonium (1) and adamantanealkylammonium (2) that we refer to as a two-faced guest because it contains two distinct binding epitopes. We find that the presence of the two-faced guests-just as is observed for protein targeting in vivo-dictates the kinetic pathway that the system follows toward equilibrium. The influence of two-faced guest structure, cation concentration, cation identity, and individual rate and equilibrium constants on the behavior of the system was explored by a combination of experiment and simulation. Deconstruction of this system led to the discovery of an anomalous host-guest complex (CB[6]center dot 1) whose dissociation rate constant (k(out) = 8.5 x 10(-10) s(-1)) is approximate to 100-fold slower than the widely used avidin, biotin affinity pair. This result, in combination with the analysis of previous systems which uncovered extraordinarily tight binding events (K-a >= 10(12) M-1), highlights the inherent potential of pursuing a systems approach toward supramolecular chemistry.