MEMBRANE MATRIX FOR THE HYDROLYSIS OF AMINO-ACID ESTERS WITH MARKED ENANTIOSELECTIVITY
MEMBRANE MATRIX FOR THE HYDROLYSIS OF AMINO-ACID ESTERS WITH MARKED ENANTIOSELECTIVITY
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DOI：
10.1021/ja00213a035
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发表时间：
1988-03-02
影响因子：
15
通讯作者：
MURAKAMI, Y
中科院分区：
文献类型：
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作者：
UEOKA, R;MATSUMOTO, Y;MURAKAMI, Y
长链底物（对硝基苯基n-十二烷酰基-D（L）-苯丙氨酸酯，D（L）-S12）在表面活性剂聚集体中的立体选择性水解可以通过改变反应温度、肽催化剂中的氨基酸序列和聚集体的组成来控制。首先，在N-十四酰基-L-组氨酰-L-亮氨酸（MyrHisLeu）和二烷基二甲基溴化铵（2CnBr; n=14，16）的催化体系中，S12水解的立体选择性（反映在kLa，obsd/kDa，obsd）在略高于聚集体相变的温度下升高。有趣的是，最佳温度（25 ℃）。2C 14 Br泡状体系中的对映选择性的温度（25 ° C）与拐点（25 ° C）相当一致。C）在1，6-二苯基-1，3，5-己三烯作为囊泡疏水区的探针的极化-温度依赖性中。这些结果表明，在最佳温度下，膜基质（2CnBr）的疏水微环境发生了变化，从而大大提高了立体选择性。第二，在本研究中的所有肽催化剂中，LLL-三肽N-（苄氧基-羰基）-L-苯丙氨酰基-L-组氨酰基-L-亮氨酸（Z-PheHisLeu）对于增强对映体选择性是最有效的（提供kLa，obsd/kDa，obsd=27）。此外，一个大的增强的对映体选择性的水解S12与Z-PheHisLeu在共聚集体系统中，这是由双链和单链阳离子表面活性剂。特别值得注意的是，通过加入十六烷基三甲基溴化铵（CTAB），在2C 14 Br（1 mM）的囊泡体系中S12与Z-PheHisLeu的高对映体选择性（kLa，obsd/kDa，obsd=27）显著提高，并在25 ℃下达到对映体速率常数比（kLa，obsd）=71。C在33mol%2C14Br/67mol%CTAB的共聚集体中。这些共聚集体看起来是直径为600-1600埃的大的棒状颗粒。从电子显微镜和动态光散射的结果。最后，在圆二色性实验的基础上，对手性选择性的来源进行了探讨，重点讨论了L异构体底物（L-S12）与活性三肽的拟合（Z-PheHisLeu）通过氨基酸残基的分子内相互作用具有疏水口袋对于增强对映选择性应该是极其重要的，并且随后，通过改变共聚集体的组成将疏水微环境调节至反应物的最佳配合将诱导最高的对映选择性。
The stereoselective hydrolysis of the long-chain substrate (p-nitrophenyl n-dodecanoyl-D(L)-phenylalanininate, D(L)-S12) in surfactant aggregates has been found to be easily controlled by changing the reaction temperature, amino acid sequence in peptide catalysts, and composition of the aggregates. First, the stereoselectivity (reflected in kLa,obsd/kDa,obsd) for the hydrolysis of S12 in the catalytic system of N-tetradecanoyl-L-histidyl-L-leucine (MyrHisLeu) and dialkyldimethylammonium bromide (2CnBr; n=14, 16) was elevated at temperatures somewhat higher than the aggregate phase transitions. Interestingly, the optimum temperature (25.degree. C) for enantioselectivity in the 2C14Br vesicular system was in fair agreement with the inflection point (25.degree. C) in the polarization-temperature dependence of 1,6-diphenyl-1,3,5-hexatriene as a probe in the hydrophobic region of the vesicles. These results suggest that the hydrophobic microenvironment of the membrane matrix (2CnBr) changes at the optimum temperature for the great enhancement of steroselectivity. Second, the LLL-tripeptide N-(benzyloxy-carbonyl)-L-phenylalanyl-L-histidyl-L-leucine (Z-PheHisLeu) was most efficient for the enhancement of enantioselectivity (affording kLa,obsd/kDa,obsd=27) among all the peptide catalysts in this study. Furthermore, a large enhanced enantioselectivity was obtained for the hydrolysis of S12 with Z-PheHisLeu in a coaggregate system, which was composed of the double- and single-chain cationic surfactants. Especially noteworthy is the fact that the high enantioselectivity (kLa,obsd/kDa,obsd=27) of S12 with Z-PheHisLeu in the vesicular system of 2C14Br (1 mM) was elevated dramatically by the addition of hexadecyltrimethylammonium bromide (CTAB) and reached the enantiomer rate constant ratio (kLa,obsd)=71 at 25.degree. C in coaggregates of 33 mol % 2C14Br/67 mol % CTAB. These coaggregates appear to be large and rodlike particles with diameters of 600-1600 .ANG. from electron microscopic and dynamic light-scattering results. Finally, with respect to the origin of enantioselectivity, it is emphasized on the basis of circular dichroism experiments that the fitting of the L isomer substrate (L-S12) and the active tripeptide (Z-PheHisLeu) having a hydrophobic pocket through the intramolecular interactions of amino acid residues should be extremely important to enhance the enantioselectivity and, subsequently, the adjusting of the hhdrophobic microenvironment to the optimum fit of reactants by changing the composition of coaggregates would induce the highest enantioselectivity.