D'Arrigo Paola, Tessaro Davide
Dipartimento di Chimica, Materiali ed Ingegneria Chimica Giulio Natta Politecnico di Milano, The Protein Factory, Politecnico di Milano and Università degli Studi dell'Insubria, Milano, Italy.
Methods Mol Biol. 2012;794:21-35. doi: 10.1007/978-1-61779-331-8_2.
The use of unnatural amino acids, particularly synthetic α-amino acids, for modern drug discovery research requires the availability of enantiomerically pure isomers. Starting from a racemate, one single enantiomer can be obtained using a deracemization process. The two more common strategies of deracemization are those obtained by stereoinversion and by dynamic kinetic resolution. Both techniques will be here described using as a substrate the D,L-3-(2-naphthyl)-alanine, a non-natural amino acid: the first one employing a multi-enzymatic redox system, the second one combining an hydrolytic enzyme together with a base-catalyzed substrate racemization. In both cases, the final product, L-3-(2-naphthyl)alanine, is recovered with good yield and excellent enantiomeric excess.
在现代药物发现研究中，使用非天然氨基酸，特别是合成α-氨基酸，需要获得对映体纯的异构体。从外消旋体开始，可以通过消旋化过程获得单一的对映体。两种更常见的消旋化策略是通过立体反转和动态动力学拆分获得的。这里将以非天然氨基酸D,L-3-(2-萘基)-丙氨酸为底物描述这两种技术：第一种采用多酶氧化还原系统，第二种将水解酶与碱催化的底物消旋化相结合。在这两种情况下，最终产物L-3-(2-萘基)丙氨酸都能以良好的产率和优异的对映体过量回收。
