Institute of Systems Biology and Bioinformatics, National Central University, Jhong-Li, Taiwan 320, Taiwan.
Phys Chem Chem Phys. 2009 Nov 14;11(42):9744-50. doi: 10.1039/b907763d. Epub 2009 Aug 20.
Chiral separation is an important issue in pharmaceutical research and industries, because most organic compounds and biological molecules, including many drugs and food additives, are chiral compounds. DNA aptamers are a new group of chiral selectors; however, there still exists deficiencies in the understanding of the molecular basis of their chiral recognition. Herein, a comparative study of the DNA aptamer binding with L-argininamide (L-Arm) and its enantiomer (D-Arm) is investigated by spectroscopic and calorimetric methods. The effect of various experimental conditions such as temperature, pH and salt concentration on the L-Arm and D-Arm binding properties was studied in order to provide information about the chiral recognition mechanism of the DNA aptamer. An isothermal titration calorimetry study reveals that both L-Arm and D-Arm binding with the aptamer are enthalpy driven and entropy cost processes. The protonated amino group of both L-Arm and D-Arm participates in electrostatic interaction and this interaction is stronger for D-Arm than L-Arm binding with the aptamer. From the opposite behavior of the heat capacity change of the two enantiomers, we could suggest that L-Arm and D-Arm bind at different binding sites of the aptamer, resulting in different conformations of the binding complexes. In the binding mechanism, electrostatic interaction provided by the protonated amino group with the aptamer and the conformational change of the nucleic acid upon binding are major processes involved for chiral recognition in the DNA aptamer. This study provides information on chiral separation of D- and L-argininamide by the aptamer, which can be successfully achieved by varying the operation temperature based on the opposite heat capacity dependence of the enantiomers binding with the DNA.
手性分离是药物研究和工业中的一个重要问题，因为大多数有机化合物和生物分子，包括许多药物和食品添加剂，都是手性化合物。DNA 适体是一类新的手性选择体；然而，对于它们手性识别的分子基础的理解仍然存在不足。在此，通过光谱和量热法研究了 DNA 适体与 L-精氨酸酰胺（L-Arm）及其对映体（D-Arm）的结合。研究了温度、pH 值和盐浓度等各种实验条件对 L-Arm 和 D-Arm 结合特性的影响，以期为 DNA 适体的手性识别机制提供信息。等温滴定量热法研究表明，L-Arm 和 D-Arm 与适体的结合均为焓驱动和熵成本过程。L-Arm 和 D-Arm 的质子化氨基均参与静电相互作用，且 D-Arm 与适体的相互作用强于 L-Arm。从两种对映体热容变化的相反行为，我们可以推测 L-Arm 和 D-Arm 结合在适体的不同结合位点，导致结合复合物的不同构象。在结合机制中，与适体的静电相互作用以及结合时核酸的构象变化是 DNA 适体手性识别的主要过程。该研究为 DNA 适体对手性分离 D-和 L-精氨酸酰胺提供了信息，可通过基于对映体与 DNA 结合的相反热容依赖性来改变操作温度来实现。
