Boger J, Knowles J R
Ciba Found Symp. 1977(60):225-42. doi: 10.1002/9780470720424.ch13.
Inspection of the active sites of the many enzymes whose structures are known at high resolution leads to the unsurprising conclusion that an enzyme may provide an environment that exquisitely stabilizes the transition state for an elementary catalytic step that is expected to be difficult. In an effort both to mimic such an environment and to have the opportunity of investigating the thermodynamic and kinetic consequences of juxtaposing polar and non-polar loci in the same molecule, we have synthesized several specifically functionalized alpha-cyclodextrins. One of these is designed to stabilize the trigonal bipyramidal transition state for an in-line displacement at the phosphorus of a phosphate monoester. This cyclodextrin contains three symmetrically disposed ammonium groups on the 'top' (at C-6) of the hydrophobic cavity formed by the hexa-glucose torus and the remaining 15 hydroxy groups are methylated. The thermodynamic consequences of adjacent hydrophobic and hydrogen-bonding and/or electrostatic binding sites are investigated using several charged and uncharged ligands. The feasibility of building host species explicitly to stabilize reaction transition states is discussed.
对许多结构已得到高分辨率解析的酶的活性位点进行检查，会得出一个不出意料的结论：酶可能提供了一种环境，能极其精确地稳定一个预期会很困难的基本催化步骤的过渡态。为了模拟这样的环境，并获得研究同一分子中极性位点与非极性位点并列所产生的热力学和动力学后果的机会，我们合成了几种经过特定功能化的α-环糊精。其中一种旨在稳定磷酸单酯磷原子处进行直线型取代反应时的三角双锥过渡态。这种环糊精在由六葡萄糖环面形成的疏水腔的“顶部”（C-6位）含有三个对称排列的铵基，其余15个羟基被甲基化。使用几种带电荷和不带电荷的配体研究了相邻疏水、氢键和/或静电结合位点的热力学后果。讨论了明确构建主体物种以稳定反应过渡态的可行性。
