Steric-control for the enantioselective hydrolysis of amino acid esters with membrane-bound enzyme models

Tanoue, Osamu; Baba, Manabu; Tokunaga, Yusuke; Goto, Kōichi; Matsumoto, Yōko; Ueoka, Ryuichi

doi:10.1016/s0040-4039(99)00129-x

Cited by 14 publications

(13 citation statements)

References 5 publications

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“…In the course of our study on the enantioselective hydrolysis (deacylation) of amino acid esters with the functional molecular assemblies composed of surfactants and reactive species, we emphasized that the stereochemical control could be attained by changing the composition of the coaggregates 1-4) and regulating ionic strength 5,6) and temperature. 7,8) Furthermore, since cyclodextrins (CyDs) have been noted as useful enzyme mimics, 9-12) we employed CyDs as host molecules and a markedly high stereoselectivity was attained in the diastereoselective deacylation of dipeptide esters.…”

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confidence: 99%

Cyclodextrin-Mediated Deacylation of Amino Acid Esters with Marked Stereoselectivity.

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Nakashima

Tanoue

et al. 2002

CHEMICAL & PHARMACEUTICAL BULLETIN

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Stereoselective hydrolysis of amino acid esters have attracted considerable attention in connection with understanding the origins of the stereoselectivity observed with proteolytic enzymes. In the course of our study on the enantioselective hydrolysis (deacylation) of amino acid esters with the functional molecular assemblies composed of surfactants and reactive species, we emphasized that the stereochemical control could be attained by changing the composition of the coaggregates 1-4) and regulating ionic strength 5,6) and temperature. 7,8) Furthermore, since cyclodextrins (CyDs) have been noted as useful enzyme mimics, 9-12) we employed CyDs as host molecules and a markedly high stereoselectivity was attained in the diastereoselective deacylation of dipeptide esters.13) On the other hand, Ueno reported the high D-enantiomer-selective deacylation of amino acid esters mediated by modified b-CyDs.14) However, little has been known about the significant enantioselectivity for the deacylation of amino acid esters with unmodified CyDs. 15) In this study, we report the successful experimental results with marked enantioselectivity for the deacylation of Z-D(L)-amino acid esters (N-(benzyloxycarbonyl)-D(L)-amino acid pnitrophenyl esters) as mediated by unmodified CyDs, and the computer modeling (molecular mechanics) studies on the inclusion complexes of g-CyD with the specific substrates are also presented. Results and DiscussionWith respect to the enantioselective hydrolysis (deacyla-Leu, Phe and Trp-PNP) mediated by unmodified a-, b-and g-CyDs, the kinetic parameters obtained on the basis of the MichaelisMenten principle, the binding constant (K b ) for the formation of CyD-substrate complex and the rate constant (k 2 ) for the deacylation of substrate by CyD, are summarized in Table 1-3. The noteworthy aspects are as follows: (a) Overall, the deacylation mediated by a-CyD was favorable for all of the L-enantiomeric substrates (reflected in k 2 K b , L/Dϭ1.5-1.7), though the K b for D-isomer of Phe substrate and k 2 values for D-isomer of Ala substrate were larger than those for the corresponding L-isomers. (b) In the case of the reaction by bCyD, L-enantiomer-selectivity was also observed for the deacylation of Ala, Leu and Phe substrates (L/Dϭ1.5-3.2), while D-enantiomeric selectivity (D/Lϭ1.4) was observed for the deacylation of Trp substrate. (c) Relatively higher L-enantioselectivity was obtained in the deacylation mediated by gCyD (L/Dϭ2.6-9.0). Most remarkably, the highest enantioselectivity (L/Dϭ9.0) was attained for the deacylation of Ala substrate. Furthermore, it was also attractive that this fairly high enantioselectivity (L/Dϭ9.0) could be mainly originated in the deacylation process of substrates, because it was reflected by a fairly large k 2 L /k 2 D value (7.4) and a smallOn the other hand, Table 4 shows the results of energies for the inclusion complexes on Z-D(L)-Ala-PNP having different shapes with g-CyD calculated by molecular mechanics with water solvent effects. It was suggested that the con...

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confidence: 99%

Cyclodextrin-Mediated Deacylation of Amino Acid Esters with Marked Stereoselectivity.

Goto

Nakashima

Tanoue

et al. 2002

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…In extensive studies carried out by Ueoka, Ohkubo and collaborators, 147,[160][161][162][163][164] the effect of vesicle-membrane-embedded short peptides on the rate of hydrolysis of membrane-bound activated amino acid esters was investigated, as summarized by Davie et al 165 Using as vesicle-forming amphiphile di-ntetradecyldimethylammonium bromide, vesicle membraneembedded Z-L-Leu-L-His-OH or Z-L-Phe-L-His-L-Leu-OH catalyzed the hydrolysis of p-nitrophenyl N-dodecanoyl-phenylalaninate at pH E 7.7 enantioselectively (Fig. 6A).…”

Section: Co-localization Of Reactants and Organic Catalysts On Or Wit...mentioning

confidence: 99%

“…147 The L-enantiomer of the ester reacted faster than the D-enantiomer. 147,164 Based on 1 H NMR measurements 162 (and molecular dynamics simulations 166 ) a model was presented for explaining the observed enantioselectivity which originates from (i) an optimal conformation of the peptide catalysts within the vesicle membrane, 147,163 and (ii) an optimal interaction between the membraneembedded L-enantiomer of the substrate and the peptide catalyst (Fig. 6B).…”

Section: Co-localization Of Reactants and Organic Catalysts On Or Wit...mentioning

confidence: 99%

Emergent properties arising from the assembly of amphiphiles. Artificial vesicle membranes as reaction promoters and regulators

et al. 2014

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This article deals with artificial vesicles and their membranes as reaction promoters and regulators. Among the various molecular assemblies which can form in an aqueous medium from amphiphilic molecules, vesicle systems are unique. Vesicles compartmentalize the aqueous solution in which they exist, independent on whether the vesicles are biological vesicles (existing in living systems) or whether they are artificial vesicles (formed in vitro from natural or synthetic amphiphiles). After the formation of artificial vesicles, their aqueous interior (the endovesicular volume) may become - or may be made - chemically different from the external medium (the exovesicular solution), depending on how the vesicles are prepared. The existence of differences between endo- and exovesicular composition is one of the features on the basis of which biological vesicles contribute to the complex functioning of living organisms. Furthermore, artificial vesicles can be formed from mixtures of amphiphiles in such a way that the vesicle membranes become molecularly, compositionally and organizationally highly complex, similarly to the lipidic matrix of biological membranes. All the various properties of artificial vesicles as membranous compartment systems emerge from molecular assembly as these properties are not present in the individual molecules the system is composed of. One particular emergent property of vesicle membranes is their possible functioning as promoters and regulators of chemical reactions caused by the localization of reaction components, and possibly catalysts, within or on the surface of the membranes. This specific feature is reviewed and highlighted with a few selected examples which range from the promotion of decarboxylation reactions, the selective binding of DNA or RNA to suitable vesicle membranes, and the reactivation of fragmented enzymes to the regulation of the enzymatic synthesis of polymers. Such type of emergent properties of vesicle membranes may have been important for the prebiological evolution of protocells, the hypothetical compartment systems preceding the first cells in those chemical and physico-chemical processes that led to the origin of life.

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“…[1][2][3][4][5] In the course of our study on the stereoselective hydrolysis (deacylation) of amino acid and dipeptide esters with the functional molecular assemblies composed of synthetic surfactants and reactive species, we emphasized that the stereochemical (enantiomeric and diastereomeric substrates) control could be attained by changing the composition of the coaggregates [6][7][8] and regulating ionic strength 9) and temperature. 10,11) Especially, an extremely high enantioselectivity was attained at the optimum composition of coaggregate. 6) However, the values of k t and k s (the first-order rate constants with and without the peptide catalyst, respectively) are fairly close for the enantioselective hydrolysis in the aggregate systems of synthetic surfactants.…”

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confidence: 98%

Steric-Control for the Enantioselective Hydrolysis of Amino Acid Esters in Hybrid Membrane Systems.

Tanoue

Ichihara

Goto

et al. 2003

CHEMICAL & PHARMACEUTICAL BULLETIN

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Stereoselective reactions have attracted considerable attention in connection with understanding the origins of the stereoselectivity observed with proteolytic enzymes. [1][2][3][4][5] In the course of our study on the stereoselective hydrolysis (deacylation) of amino acid and dipeptide esters with the functional molecular assemblies composed of synthetic surfactants and reactive species, we emphasized that the stereochemical (enantiomeric and diastereomeric substrates) control could be attained by changing the composition of the coaggregates [6][7][8] and regulating ionic strength 9) and temperature.10,11) Especially, an extremely high enantioselectivity was attained at the optimum composition of coaggregate. 6)However, the values of k t and k s (the first-order rate constants with and without the peptide catalyst, respectively) are fairly close for the enantioselective hydrolysis in the aggregate systems of synthetic surfactants. Then, it is impossible to disregard the errors of k t and k s values when we discuss catalytic activities of the artificial membranes bound enzyme on the basis of k a,obsd values.In this study, we employed native phospholipids instead of synthetic surfactants for the hydrolysis of amino acid esters12) with tripeptide (Z-PheHisLeu) 12) in the coaggregate systems. The advantage of this experiment should enable to evaluate of the catalytic activities directly on the basis of k a,obsd values because of the large difference of the k t and k s values, that is, the k t /k s ratios were above 30 and 4 folds for the L-and D-substrates, respectively.Recently, in the course of our study on artificial membranes composed of native phospholipids, very useful knowledges for medical engineering applications in vitro and in vivo have been obtained. For example, artificial lipid membranes were used as a drug carrier in drug delivery systems, such as 1,3-bis(2-chloroethyl)-1-nitrosourea encapsulated in hybrid liposomes (artificial membranes) which should be effective against malignant glioma in vitro and in vivo. 13)Moreover, the artificial membranes themselves were found to be useful as a new type of anticancer drug without side effects. 14,15) In this study, we report on the remarkable effects (composition of hybrid membranes and reaction temperature) on the enantioselective hydrolysis of C 12 -D(L)-Phe-PNP catalyzed by Z-PheHisLeu in the hybrid membranes composed of phospholipid (DMPC) and nonionic surfactant (C 12 (EO) 8 ) at pH 7.4. The relations between the enantioselectivity and the microenvironment of the reaction fields are discussed. Results and DiscussionThe composition dependence of coaggregates on the enantioselective hydrolysis of C 12 -D(L)-Phe-PNP catalyzed by Z-PheHisLeu was investigated in hybrid membranes of DMPC/C 12 (EO) 8 , as shown in Fig. 1. The concentration of C 12 (EO) 8 is expressed as mol% of total lipids. Both the second-order rate constants (k a,obsd ) and enantioselectivity (k ; 4-22-1 Ikeda, Kumamoto 860-0082, Japan. Received November 5, 2002; accepted November 26, 20...

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Steric-control for the enantioselective hydrolysis of amino acid esters with membrane-bound enzyme models

Cited by 14 publications

References 5 publications

Cyclodextrin-Mediated Deacylation of Amino Acid Esters with Marked Stereoselectivity.

Cyclodextrin-Mediated Deacylation of Amino Acid Esters with Marked Stereoselectivity.

Emergent properties arising from the assembly of amphiphiles. Artificial vesicle membranes as reaction promoters and regulators

Steric-Control for the Enantioselective Hydrolysis of Amino Acid Esters in Hybrid Membrane Systems.

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