Frycák Petr, Schug Kevin A
Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, Texas 76019-0065, USA.
Chirality. 2009 Nov;21(10):929-36. doi: 10.1002/chir.20691.
Because of the generally different interaction of enantiomers with biological systems, there has been an ever increasing demand for artificial highly enantioselective systems that can facilitate separation processes involved in the research and development of enantiomerically pure drugs. Such systems may be discovered by large-scale screening of compound libraries which warrants rapid and cost-efficient screening methods. Here, we demonstrate enantioselectivity determination for systems of cinchona alkaloid carbamates and N-blocked amino acids using HPLC-MS and the recently developed dynamic titration technique (Frycák P, Schug KA. Anal Chem 2008;80:1385-1393). A mixture of nine N-blocked amino acids (either D or L enantiomers) was separated on a reversed-phase column with cinchona alkaloid carbamates added postcolumn. Dissociation constants of the observed noncovalent complexes were determined from the HPLC-MS data. Enantioselectivity was then calculated from the dissociation constants, pointing out the best performing systems. For these systems, apparent dissociation constants were measured for the whole range of enantiomeric composition and were shown to obey a proposed theoretical model.
由于对映体与生物系统的相互作用通常存在差异，因此对人工高对映选择性系统的需求不断增加，这些系统有助于对映体纯药物研发过程中的分离过程。此类系统可通过对化合物库进行大规模筛选来发现，这就需要快速且经济高效的筛选方法。在此，我们使用高效液相色谱-质谱联用技术（HPLC-MS）以及最近开发的动态滴定技术（Frycák P，Schug KA。分析化学2008；80：1385 - 1393），证明了金鸡纳生物碱氨基甲酸盐与N-保护氨基酸系统的对映选择性。将九种N-保护氨基酸（D或L对映体）的混合物在反相柱上分离，柱后添加金鸡纳生物碱氨基甲酸盐。根据HPLC-MS数据确定观察到的非共价复合物的解离常数。然后根据解离常数计算对映选择性，指出性能最佳的系统。对于这些系统，在整个对映体组成范围内测量了表观解离常数，并证明其符合所提出的理论模型。
