Université Bordeaux, CBMN, UMR 5248, Institut Européen de Chimie Biologie, 2 rue Escarpit, 33607 Pessac, France.
J Am Chem Soc. 2012 Jul 11;134(27):11282-8. doi: 10.1021/ja304322c. Epub 2012 Jun 28.
Helically folded molecular capsules based on oligoamide sequences of aromatic amino acids which are capable of binding tartaric acid in organic solvents with high affinity and diastereoselectivity have been synthesized, and their structures and binding properties investigated by (1)H NMR, X-ray crystallography, circular dichroism, and molecular modeling. We found that elongating the helices at their extremities by adding monomers remote from the tartaric binding site results in a strong increase of the overall helix stability, but it does not influence the host-guest complex stability. The effect of this elongation on the binding and release rates of the guest molecules follows an unexpected non-monotonous trend. Three independent observations (direct monitoring of exchange over time, 2D-EXSY NMR, and molecular modeling) concur and show that guest exchange rates tend to first increase upon increasing helix length and then decrease when helix length is increased further. This investigation thus reveals the complex effects of adding monomers in a helically folded sequence on a binding event that occurs at a remote site and sheds light on possible binding and release mechanisms.
基于芳香族氨基酸寡肽序列的螺旋折叠分子胶囊能够在有机溶剂中与酒石酸高亲和力和对映选择性结合。我们已经合成了这些分子胶囊，并通过（1）H NMR、X 射线晶体学、圆二色性和分子建模研究了它们的结构和结合性质。我们发现，通过在远离酒石酸结合位点的位置添加单体来延长螺旋的末端，会导致整体螺旋稳定性的强烈增加，但不会影响主客体配合物的稳定性。这种延伸对客体分子的结合和释放速率的影响遵循一种出人意料的非单调趋势。三个独立的观察结果（随时间直接监测交换、2D-EXSY NMR 和分子建模）一致表明，客体交换速率在增加螺旋长度时首先增加，然后在进一步增加螺旋长度时减小。这项研究揭示了在远离结合部位的结合事件中，在螺旋折叠序列中添加单体对结合的复杂影响，并阐明了可能的结合和释放机制。
