Billiot Alexander, Fang Yayin, Morris Kevin F
Department of Physical and Environmental Sciences, Texas A&M University-Corpus Christi, 6300 Ocean Drive, Corpus Christi, TX 78412, USA.
Department of Biochemistry and Molecular Biology, College of Medicine, Howard University. 520 W Street NW, Washington DC 20059, USA.
Open J Phys Chem. 2019 Nov;9(4):221-240. doi: 10.4236/ojpc.2019.94014. Epub 2019 Nov 29.
The enantiomers of chiral drugs often have different potencies, toxicities, and biochemical properties. Therefore, the FDA and other worldwide regulatory agencies require manufactures to test and prove the enantiomeric purity of chiral drugs. Amino acid based molecular micelles (AABMM) have been used in chiral CE separations since the 1990's because of their low environmental impact and because their properties can easily be tuned by changing the amino acids in the chiral surfactant headgroups. Using molecular dynamics simulations to investigate the structures and properties of AABMM is part of an ongoing study focusing on investigating and elucidating the factors responsible for chiral recognition with AABMM. The results will be useful for the proper design and selection of more efficient chiral selectors. The micelles investigated contained approximately twenty covalently linked surfactant monomers. Each monomer was in turn composed of an undecyl hydrocarbon chain bound to a dipeptide headgroup containing of all combinations of L-Alanine, L-Valine, and L-Leucine. These materials are of interest because they are effective chiral selectors in capillary electrophoresis separations. Molecular dynamics simulation analyses were used to investigate how the sizes and positions of the headgroup amino acid R-groups affected the solvent accessible surface areas of each AABMM chiral center. In addition, headgroup dihedral angle analyses were used to investigate how amino acid R-group size and position affected the overall headgroup conformations. Finally, distance measurements were used to study the structural and conformational flexibilities of each AABMM headgroup. All analyses were performed in the context of a broader study focused on developing structure-based predictive tools to identify the factors responsible for (a) self-assembly, (b) function, (c) higher ordered structure and (d) molecular recognition of these amino acid based molecular micelles.
手性药物的对映体通常具有不同的效能、毒性和生化特性。因此，美国食品药品监督管理局（FDA）和全球其他监管机构要求制造商测试并证明手性药物的对映体纯度。自20世纪90年代以来，基于氨基酸的分子胶束（AABMM）就已用于手性毛细管电泳分离，这是因为它们对环境的影响较小，并且其性质可以通过改变手性表面活性剂头基中的氨基酸轻松调节。使用分子动力学模拟来研究AABMM的结构和性质是一项正在进行的研究的一部分，该研究专注于调查和阐明导致AABMM手性识别的因素。研究结果将有助于更合理地设计和选择更高效的手性选择剂。所研究的胶束包含大约二十个共价连接的表面活性剂单体。每个单体又由一条与二肽头基相连的十一烷基烃链组成，该二肽头基包含L-丙氨酸、L-缬氨酸和L-亮氨酸的所有组合。这些材料之所以受到关注，是因为它们是毛细管电泳分离中有效的手性选择剂。分子动力学模拟分析用于研究头基氨基酸R基团的大小和位置如何影响每个AABMM手性中心的溶剂可及表面积。此外，头基二面角分析用于研究氨基酸R基团的大小和位置如何影响整个头基构象。最后，距离测量用于研究每个AABMM头基的结构和构象灵活性。所有分析都是在一项更广泛研究的背景下进行的，该研究专注于开发基于结构的预测工具，以识别导致这些基于氨基酸的分子胶束（a）自组装、（b）功能、（c）高阶结构和（d）分子识别的因素。
