Enzymatic Catalysts in Organic Synthesis

Wong, C.-H.

doi:10.1126/science.2658059

Cited by 264 publications

(51 citation statements)

References 103 publications

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“…The concentrations of acyl donors (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16), acyl acceptors (a-c), and enzymes were 1 mM, 20 mM, and 5 mM, respectively. The progress of the peptide coupling reaction was monitored by HPLC under the following conditions: isocratic elution at 1 ml/min, 0.1% trifluoroacetic acid/acetonitrile.…”

Section: Methodsmentioning

confidence: 99%

“…Especially, peptide synthesis using protease-catalyzed reverse reaction has been extensively studied with a variety of amino acids and peptide derivatives as coupling components. [2][3][4][5][6][7][8] It has been reported that the protease-catalyzed peptide synthesis is superior to the chemical coupling method because it is highly stereoselective, racemization-free, and requires less side-chain protection. The major drawback of the enzymatic method, however, is the respective substrate specificity.…”

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confidence: 99%

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Atlantic Cod Trypsin-Catalyzed Peptide Synthesis with Inverse Substrates as Acyl Donor Components

Fuchise

Kishimura

Zhi-yong

et al. 2010

CHEMICAL & PHARMACEUTICAL BULLETIN

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A large number of biologically active peptides have been isolated recently from bacterial, fungal, plant and animal sources and characterized in some detail. In particular, shortsequence peptides play important roles in the sensory appreciation of food toward four basic taste sensations (sweet, bitter, sour and salty). 1) Such peptides sometimes contain Damino acid and other unusual amino acids. Synthetic chemistry has witnessed remarkable progress with the development of novel biologically active peptides. Enzymatic peptide synthesis has emerged as a powerful approach to the preparation of short sequences. Especially, peptide synthesis using protease-catalyzed reverse reaction has been extensively studied with a variety of amino acids and peptide derivatives as coupling components. [2][3][4][5][6][7][8] It has been reported that the protease-catalyzed peptide synthesis is superior to the chemical coupling method because it is highly stereoselective, racemization-free, and requires less side-chain protection. The major drawback of the enzymatic method, however, is the respective substrate specificity. Thus, the application of proteases for peptide synthesis has not been fully investigated synthetic possiblity of a number of biologically significant peptides containing D-amino acid or other unusual amino acids. A few previous reports have shown the enzymatic condensation of noncorded amino acids, 9,10) peptide mimetics, 11) peptide conjugates, 12) and D-amino acid. 13) Previously, we reported that the inverse substrates such as p-amidino-14) and p-guanidinophenyl esters [15][16][17] behave as specific substrates for trypsin and trypsin-like enzymes and allow the specific introduction of an acyl group carrying a non-specific residue into the enzymatic active site. The characteristics of inverse substrates suggested that they are useful for enzymatic peptide synthesis. [18][19][20][21][22][23][24] Many studies on the characterization of trypsins from cold-adapted species have been reported. 25) These trypsins display substantially higher catalytic efficiency than their mammalian counterparts. [25][26][27][28][29][30][31][32][33] We previously reported the chum salmon trypsin-catalyzed synthesis of peptides using inverse substrates. 23,24) We had obtained commercially available Atlantic cod trypsin at almost the same time. We are interested in comparing of the catalytic efficiency of Atlantic cod trypsin with chum salmon trypsin. In the present work, we investigated Atlantic cod trypsin-catalyzed peptide synthesis using p-amidino-and p-guanidinophenyl esters of N atert-butyloxycarbonyl (Boc)-amino acid as acyl donor components with two types of acyl acceptors. We have found that Atlantic cod trypsin-catalyzed peptide synthesis of the Damino acid and b-amino acid-containing products is more efficient than chum salmon trypsin-catalyzed synthesis. Results and DiscussionThe kinetic constants for the trypsin-catalyzed hydrolysis of synthetic inverse substrates were analyzed on the basis of the following scheme.Where: Eϭe...

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

Atlantic Cod Trypsin-Catalyzed Peptide Synthesis with Inverse Substrates as Acyl Donor Components

Fuchise

Kishimura

Zhi-yong

et al. 2010

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…[10][11][12][13][14][15] The protease-catalyzed peptide synthesis is superior to the chemical coupling method. The method requires less-side chain protection than the chemical coupling method.…”

Section: )mentioning

confidence: 99%

Trypsin-Catalyzed Synthesis of Dipeptide Containing .ALPHA.-Aminoisobutylic Acid Using p- and m-(Amidinomethyl)phenyl Esters as Acyl Donor

Sekizaki

Itoh

Shibuya

et al. 2008

CHEMICAL & PHARMACEUTICAL BULLETIN

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Sterically hindered a-amino acid such as the a-aminoisobutylic acid (Aib, 2-methylalanine) is one of the constituent of naturally occurring antibiotics.1-4) Peptides containing Aib are of interest as the model for conformational analysis of the peptide backbone (formation of a-or 3 10 -helices, or b-turns).5,6) However, the introduction of Aib into a peptide is difficult, 4,7,8) because the reactivity of sterically hindered a,a-disubstituted amino acid is much lower than that of typical a-amino acids. New chemical coupling reagent, 2-chloro-1,3-dimethylimidazolidium hexafluorophosphate, (CIP), for sterically hindered a,a-disubstituted amino acidis was developed and chemical synthesis of Alamethicin F-30 was achieved. 9)Peptide synthesis by protease-catalyzed reverse reaction has been extensively studied with a variety of amino acids and peptide derivatives as coupling. [10][11][12][13][14][15] The protease-catalyzed peptide synthesis is superior to the chemical coupling method. The method requires less-side chain protection than the chemical coupling method. A most serious drawback of the enzymatic method, however, is the respective substrate specificity. Thus, the application of proteases for peptide synthesis has not been fully exploited for possible synthesis of a number of biologically important peptides containing Damino acid or other unusual amino acid.In a previous paper, we reported that the p-amidinophenyl and p-guanidinophenyl esters behave as specific substrates for trypsin and trypsin-like enzymes such as thrombin and plasmin, etc. [16][17][18] In these esters the site-specific groups (charged amidinium and guanidinium) for the enzyme are included in the leaving-group portion instead of being in the acyl moiety. Such a substrate was termed "inverse substrate" by us.16) The esters provided a novel method for the specific introduction of an acyl group for a wide variety of acyl groups into a trypsin active site, and such acyl enzymes have proven to be useful for the peptide coupling. 13,14,[19][20][21][22][23][24][25][26][27][28] We also reported that a,a-dialkyl amino acid p-(guanidinomethyl)phenyl esters were useful substrates for enzymatic peptides synthesis containing such a hindered amino acid. 21)Recently, we reported that preparation of new two series inverse substrates such as N-Boc-amino acid p-and m-(amidinomethyl)phenyl esters. 29) In the present work, we investigated trypsin-catalyzed peptide synthesis using these synthetic substrates as acyl donor components. Comparison was made between two trypsins of different origin (bovine and Streptomyces griseus (SG) trypsin) as the catalyst for peptide synthesis as shown in Chart 1. Trypsin-Catalyzed Peptide Coupling ReactionThe trypsin-catalyzed peptide coupling reaction has been studied by using synhetic inverse substrates (1a-h, 2a-c) as acyl donors (Fig. 1) was examined in dimethyl sulfoxide (DMSO) or N,N-dimethylformamide (DMF) as a co-solvent. The reaction was also evaluated under the condition where the pH of the medium was changed and the ...

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“…[1][2][3][4][5][6] In recent years, biocatalytic methodology, once thought to be an esoteric area and largely confined to the laboratories with necessary expertise, has now become a primary activity of research in most of the leading research laboratories working in the areas of both organic, bioorganic and medicinal chemistry. [7][8][9][10][11][12][13][14] Despite the very useful and attractive applications of chemico-enzymatic methodology in synthetic organic chemistry, there still exists some apprehension amongst organic chemists with respect to handling of the enzymes and experimental techniques. Also most of the commercially available enzymes are expensive.…”

Section: Introductionmentioning

confidence: 99%

Applications of liver acetone powders in enantioselective synthesis

Basavaiah¹

2001

Arkivoc

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Applications of liver acetone powders (crude enzymes) as possible substitutes for purified enzyme preparations, hydrolases, in enantioselective organic transformations have been systematically investigated. (1R, 2R)-2-(4-Alkylphenoxy)cyclohexan-1-ols, (1R, 2R)-& (1S, 2S)-2-nitroxycyclohexan-1-ols, (1R, 2S)-2-arylcyclohexan-1-ols, (3R, 4R)-6-methyl-3-phenylhept-1-en-4-ol, and (R)-1-(naphth-1-yl)ethanol have been synthesized in enantiomerically pure form via the enantioselective hydrolysis of the corresponding racemic acetates mediated by liver acetone powders.

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Enzymatic Catalysts in Organic Synthesis

Cited by 264 publications

References 103 publications

Atlantic Cod Trypsin-Catalyzed Peptide Synthesis with Inverse Substrates as Acyl Donor Components

Atlantic Cod Trypsin-Catalyzed Peptide Synthesis with Inverse Substrates as Acyl Donor Components

Trypsin-Catalyzed Synthesis of Dipeptide Containing .ALPHA.-Aminoisobutylic Acid Using p- and m-(Amidinomethyl)phenyl Esters as Acyl Donor

Applications of liver acetone powders in enantioselective synthesis

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