Tomas Salvador, Milanesi Lilia
School of Biological and Chemical Sciences, Birkbeck, University of London, Malet Street, London WC1E 7HX, UK.
J Am Chem Soc. 2009 May 13;131(18):6618-23. doi: 10.1021/ja900561j.
Biomolecular and artificial receptors are typically designed to exploit the hydrophobic effect in order to enhance the stability of receptor-ligand complexes in water. For example, artificial receptors are often built around hydrophobic cavities. These receptors exploit the hydrophobic effect toward ligand recognition, but the structure of the binding site requires a rigid framework to overcome the hydrophobic effect-driven tendency to collapse. Here we present an artificial receptor that exploits the hydrophobic effect to define its structure in water. The receptor is based on amphiphilic building blocks that assemble into micelle-like aggregates of a very high stability, attributed to the unusual shape of the amphiphile: a relatively rigid molecule composed of a large hydrophobic segment, based on the cholesterol molecule, and a very large headgroup build around a Zn-metalloporphyrin moiety. The assemblies, persistent down to the nanomolar range, are better described as self-assembled nanoparticles. Within the nanoparticle-water interface, Zn-metalloporphyrin moieties form multiple binding sites that specifically bind ligands bearing basic nitrogen atoms. The nanoparticles show enhanced binding affinity relative to a model receptor that does not self-assemble. Structurally related ligands show a correlation between the enhancement of binding and the octanol/water partition coefficient, log P, suggesting that the desolvation of binding sites is the main driving force for the enhancement of binding affinity at the nanoparticle-water interface. In addition, the highest affinity observed for the ditopic ligands relative to the monotopic ligands is evidence of a multivalent effect operating within this type of receptors. The nanoparticle readily deassembles upon addition of water-miscible organic solvents, such as methanol, or in the presence of detergents. This approach toward self-assembled receptors can be easily adapted to the development of differential receptors by the simple expedient of mixing slightly different amphiphiles (i.e., different metals in the porphyrin ring for the amphiphiles described here) in variable proportions.
生物分子受体和人工受体通常被设计用于利用疏水效应，以增强受体 - 配体复合物在水中的稳定性。例如，人工受体常常围绕疏水腔构建。这些受体利用疏水效应进行配体识别，但结合位点的结构需要一个刚性框架来克服疏水效应驱动的塌陷趋势。在此，我们展示一种利用疏水效应在水中确定其结构的人工受体。该受体基于两亲性构建模块，这些模块组装成具有非常高稳定性的胶束状聚集体，这归因于两亲分子的特殊形状：一个相对刚性的分子，由基于胆固醇分子的大疏水片段和围绕锌金属卟啉部分构建的非常大的头部基团组成。这些聚集体在纳摩尔范围内仍保持稳定，更适合描述为自组装纳米颗粒。在纳米颗粒 - 水界面内，锌金属卟啉部分形成多个结合位点，特异性结合带有碱性氮原子的配体。相对于未自组装的模型受体，这些纳米颗粒表现出增强的结合亲和力。结构相关的配体显示结合增强与正辛醇/水分配系数log P之间存在相关性，这表明结合位点的去溶剂化是纳米颗粒 - 水界面处结合亲和力增强的主要驱动力。此外，相对于单位点配体，双位点配体观察到的最高亲和力证明了在这类受体中存在多价效应。加入与水混溶的有机溶剂（如甲醇）或在存在洗涤剂的情况下，纳米颗粒很容易解体。通过简单地按可变比例混合略有不同的两亲分子（即此处描述的两亲分子卟啉环中的不同金属），这种自组装受体的方法可以很容易地应用于差异受体的开发。
