- Noncovalently Functionalized Commodity Polymers as Tailor-Made Additives for Stereoselective Crystallization
-
Stereoselective inhibition of the nucleation and crystal growth of one enantiomer aided by “tailor-made” polymeric additives is an efficient method to obtain enantiopure compounds. However, the conventional preparation of polymeric additives from chiral monomers are laborious and limited in structures, which impedes their rapid optimization and applicability. Herein, we report a “plug-and-play” strategy to facilitate synthesis by using commercially available achiral polymers as the platform to attach various chiral small molecules as the recognition side-chains through non-covalent interactions. A library of supramolecular polymers made up of two vinyl polymers and six small molecules were applied with seeds in the selective crystallization of seven racemates in different solvents. They showed good to excellent stereoselectivity in yielding crystals with high enantiomeric purities in conglomerates and racemic compound forming systems. This convenient, low-cost modular synthesis strategy of polymeric additives will allow for high-efficient, economical resolution of various racemates on different scales.
- Wan, Xinhua,Wang, Zhaoxu,Ye, Xichong,Zhang, Jie
-
supporting information
p. 20243 - 20248
(2021/08/09)
-
- Highly selective synthesis of d-amino acids from readily available l-amino acids by a one-pot biocatalytic stereoinversion cascade
-
d-Amino acids are key intermediates required for the synthesis of important pharmaceuticals. However, establishing a universal enzymatic method for the general synthesis of d-amino acids from cheap and readily available precursors with few by-products is challenging. In this study, we constructed and optimized a cascade enzymatic route involving l-amino acid deaminase and d-amino acid dehydrogenase for the biocatalytic stereoinversions of l-amino acids into d-amino acids. Using l-phenylalanine (l-Phe) as a model substrate, this artificial biocatalytic cascade stereoinversion route first deaminates l-Phe to phenylpyruvic acid (PPA) through catalysis involving recombinant Escherichia coli cells that express l-amino acid deaminase from Proteus mirabilis (PmLAAD), followed by stereoselective reductive amination with recombinant meso-diaminopimelate dehydrogenase from Symbiobacterium thermophilum (StDAPDH) to produce d-phenylalanine (d-Phe). By incorporating a formate dehydrogenase-based NADPH-recycling system, d-Phe was obtained in quantitative yield with an enantiomeric excess greater than 99%. In addition, the cascade reaction system was also used to stereoinvert a variety of aromatic and aliphatic l-amino acids to the corresponding d-amino acids by combining the PmLAAD whole-cell biocatalyst with the StDAPDH variant. Hence, this method represents a concise and efficient route for the asymmetric synthesis of d-amino acids from the corresponding l-amino acids.
- Zhang, Danping,Jing, Xiaoran,Zhang, Wenli,Nie, Yao,Xu, Yan
-
p. 29927 - 29935
(2019/10/01)
-
- Preparation and characterization of a new open-tubular capillary column for enantioseparation by capillary electrochromatography
-
In order to use the enantioseparation capability of cationic cyclodextrin and to combine the advantages of capillary electrochromatography (CEC) with open-tubular (OT) column, in this study, a new OT-CEC, coated with cationic cyclodextrin (1-allylimidazolium-β-cyclodextrin [AI-β-CD]) as chiral stationary phase (CSP), was prepared and applied for enantioseparation. Synthesized AI-β-CD was characterized by infrared (IR) spectrometry and mass spectrometry (MS). The preparation conditions for the AI-β-CD-coated column were optimized with the orthogonal experiment design L9(34). The column prepared was characterized by scanning electron microscopy (SEM) and elemental analysis (EA). The results showed that the thickness of stationary phase in the inner surface of the AI-β-CD-coated columns was about 0.2 to 0.5?μm. The AI-β-CD content in stationary phase based on the EA was approximately 2.77?mmol·m?2. The AI-β-CD-coated columns could separate all 14 chiral compounds (histidine, lysine, arginine, glutamate, aspartic acid, cysteine, serine, valine, isoleucine, phenylalanine, salbutamol, atenolol, ibuprofen, and napropamide) successfully in the study and exhibit excellent reproducibility and stability. We propose that the column, coated with AI-β-CD, has a great potential for enantioseparation in OT-CEC.
- Li, Yingjie,Tang, Yimin,Qin, Shili,Li, Xue,Dai, Qiang,Gao, Lidi
-
p. 283 - 292
(2019/02/05)
-
- Artificial Biocatalytic Cascade with Three Enzymes in One Pot for Asymmetric Synthesis of Chiral Unnatural Amino Acids
-
Two biocatalytic reactions, transamination catalyzed by transaminases and reductive amination catalyzed by amino acid dehydrogenases, can be used for asymmetric synthesis of optically pure unnatural amino acids. However, although transaminases show a great diversity and broad substrate spectrum, most transaminase reactions are reversible, while amino acid dehydrogenases catalyze reductive amination irreversibly but with strict substrate specificity. Accordingly, herein we developed a tri-enzyme one-pot reaction system to exploit the respective advantages of transaminases and amino acid dehydrogenases, while overcoming the disadvantages of each. In this work, representatives of all four subgroups of transaminases coupled with different amino acid dehydrogenases to produce five l- and four d- unnatural amino acid products, using ammonia and the co-enzyme NAD(P)H, which is regenerated by a robust alcohol dehydrogenase with 2-propanol as cheap cosubstrate. The complete conversion and high enantiopurity (ee > 99 %) of the products, demonstrated it as an ideal alternative for asymmetric synthesis of chiral amino acid compounds.
- Zhou, Haisheng,Meng, Lijun,Yin, Xinjian,Liu, Yayun,Xu, Gang,Wu, Jianping,Wu, Mianbin,Yang, Lirong
-
p. 6470 - 6477
(2019/11/02)
-
- Chiral Metal–Organic Framework Hollow Nanospheres for High-Efficiency Enantiomer Separation
-
Chiral ZIF-8 hollow nanospheres with d-histidine as part of chiral ligands (denoted as H-d-his-ZIF-8) were prepared for separation of (±)-amine acids. Compared to bulk d-his-ZIF-8 without a hollow cavity, the prepared H-d-his-ZIF-8 showed 15 times higher separation capacity and higher ee values of 90.5 % for alanine, 95.2 % for glutamic acid and 92.6 % for lysine, respectively.
- Wang, Xiaoshi,Zhu, Yanan,Liu, Jian,Liu, Chang,Cao, Changyan,Song, Weiguo
-
p. 1535 - 1538
(2018/06/26)
-
- Structural and enzymatic properties of mammalian D-glutamate cyclase
-
D-Glutamate cyclase (DGLUCY) is a unique enzyme that reversibly converts free D-glutamate to 5-oxo-D-proline and H2O. Mammalian DGLUCY is highly expressed in the mitochondrial matrix in the heart, and its downregulation disrupts D-glutamate and/or 5-oxo-D-proline levels, contributing to the onset and/or exacerbation of heart failure. However, detailed characterisation of DGLUCY has not yet been performed. Herein, the structural and enzymatic properties of purified recombinant mouse DGLUCY were examined. The results revealed a dimeric oligomerisation state, and both D-glutamate-to-5-oxo-D-proline and 5-oxo-D-proline-to-D-glutamate reactions were catalysed in a stereospecific manner. Catalytic activity is modulated by divalent cations and nucleotides including ATP and ADP. Interestingly, the presence of Mn2+ completely abolished the 5-oxo-D-proline-to-D-glutamate reaction but stimulated the D-glutamate-to-5-oxo-D-proline reaction. The optimum pH is ~8.0, similar to that in the mitochondrial matrix, and the catalytic efficiency for D-glutamate is markedly higher than that for 5-oxo-D-proline. These findings suggest that DGLUCY functions as a metalloenzyme that degrades D-glutamate in the mitochondrial matrix in mammalian cells. The results also provide insight into the correlation between DGLUCY enzyme activity and the physiological and pathological roles of D-glutamate and 5-oxo-D-proline in cardiac function, which is of relevance to the risk of onset of heart failure.
- Katane, Masumi,Ariyoshi, Makoto,Tateishi, Shuhei,Koiwai, Sachi,Takaku, Kaoruko,Nagai, Kenichiro,Nakayama, Kazuki,Saitoh, Yasuaki,Miyamoto, Tetsuya,Sekine, Masae,Mita, Masashi,Hamase, Kenji,Matoba, Satoaki,Homma, Hiroshi
-
-
- Chromatographic Resolution of α-Amino Acids by (R)-(3,3'-Halogen Substituted-1,1'-binaphthyl)-20-crown-6 Stationary Phase in HPLC
-
Three new chiral stationary phases (CSPs) for high-performance liquid chromatography were prepared from R-(3,3'-halogen substituted-1,1'-binaphthyl)-20-crown-6 (halogen = Cl, Br and I). The experimental results showed that R-(3,3'-dibromo-1,1'-binaphthyl)-20-crown-6 (CSP-1) possesses more prominent enantioselectivity than the two other halogen-substituted crown ether derivatives. All twenty-one α-amino acids have different degrees of separation on R-(3,3'-dibromo-1,1'-binaphthyl)-20-crown-6-based CSP-1 at room temperature. The enantioselectivity of CSP-1 is also better than those of some commercial R-(1,1'-binaphthyl)-20-crown-6 derivatives. Both the separation factors (α) and the resolution (Rs) are better than those of commercial crown ether-based CSPs [CROWNPAK CR(+) from Daicel] under the same conditions for asparagine, threonine, proline, arginine, serine, histidine and valine, which cannot be separated by commercial CR(+). This study proves the commercial usefulness of the R-(3,3'-dibromo-1,1'-binaphthyl)-20-crown-6 chiral stationary phase.
- Wu, Peng,Wu, Yuping,Zhang, Junhui,Lu, Zhenyu,Zhang, Mei,Chen, Xuexian,Yuan, Liming
-
p. 1037 - 1042
(2017/07/25)
-
- Asymmetric Transamination of α-Keto Acids Catalyzed by Chiral Pyridoxamines
-
A new type of novel chiral pyridoxamines 3a-g containing a side chain has been developed. The pyridoxamines displayed catalytic activity and promising enantioselectivity in biomimetic asymmetric transamination of α-keto acids, to give various α-amino acids in 47-90% yields with up to 87% ee's under very mild conditions. An interesting effect of the side chain on enantioselectivity was observed in the reaction.
- Lan, Xiaoyu,Tao, Chuangan,Liu, Xuliang,Zhang, Aina,Zhao, Baoguo
-
supporting information
p. 3658 - 3661
(2016/08/16)
-
- An easy 'Filter-and-Separate' method for enantioselective separation and chiral sensing of substrates using a biomimetic homochiral polymer
-
We present a polyfluorene appended with protected l-glutamic acid that exhibited a reversible α-helix/β-sheet-like conformation and helical porous fibrous morphology mimicking the super-structure of proteins. The new homochiral polymer probe enabled efficient heterogeneous enantioselective separation and chiral sensing of a wide variety of substrates from their aqueous racemic mixture using an easy 'Filter-and-Separate' method.
- Senthilkumar,Asha
-
supporting information
p. 8931 - 8934
(2015/05/27)
-
- Deracemization of amino acids by coupling transaminases of opposite stereoselectivity
-
Biocatalytic deracemization of amino acids without relying on oxidase-based deamination of an unwanted enantiomer was demonstrated by coupling a-and w-transaminases displaying opposite stereoselectivity. This strategy employs isopropylamine and a keto acid as cosubstrates and is free of generation of hydrogen peroxide which is troublesome in the conventional oxidase-based methods.
- Park, Eul-Soo,Shin, Jong-Shik
-
p. 3505 - 3509
(2015/02/19)
-
- Seven new and two known lipopeptides as well as five known polyketides: The activated production of silent metabolites in a marine-derived fungus by chemical mutagenesis strategy using diethyl sulphate
-
AD-2-1 is an antitumor fungal mutant obtained by diethyl sulfate mutagenesis of a marine-derived Penicillium purpurogenum G59. The G59 strain originally did not produce any metabolites with antitumor activities in MTT assays using K562 cells. Tracing newly produced metabolites under guidance of MTT assay and TLC analysis by direct comparison with control G59 extract, seven new (1-7) and two known (8-9) lipopeptides were isolated together with five known polyketides 10-14 from the extract of mutant AD-2-1. Structures of the seven new compounds including their absolute configurations were determined by spectroscopic and chemical evidences and named as penicimutalides A-G (1-7). Seven known compounds were identified as fellutamide B (8), fellutamide C (9), 1.-O-methylaverantin (10), averantin (11), averufin (12), nidurufin (13), and sterigmatocystin (14). In the MTT assay, 1-14 inhibited several human cancer cell lines to varying extents. All the bioassays and HPLC-photodiode array detector (PDAD)-UV and HPLC-electron spray ionization (ESI)-MS analyses demonstrated that the production of 1-14 in the mutant AD-2-1 was caused by the activated production of silent metabolites in the original G59 fungal strain. Present results provided additional examples for effectiveness of the chemical mutagenesis strategy using diethyl sulphate mutagenesis to discover new compounds by activating silent metabolites in fungal isolates.
- Wu, Chang-Jing,Li, Chang-Wei,Cui, Cheng-Bin
-
p. 1815 - 1838
(2014/06/09)
-
- Biochemical characterization of an extremely thermostable l-asparaginase from Thermococcus gammatolerans EJ3
-
Microbial l-asparaginases which catalyze the conversion of l-asparagine to l-asparate and ammonia, have been proved to be useful in medical and food industries. In the present work, a thermostable l-asparaginase was characterized from a hyperthermophilic archaeon strain, Thermococcus gammatolerans EJ3. Cloning and recombinant expression of Tco. gammatolerans l-asparaginase was performed in Escherichia coli. The recombinant enzyme was purified to homogeneity by nickel-affinity chromatography, and was characterized as a homodimer composed of two identical subunits of approximately 36.5 kDa. The optimum pH and temperature were 8.5 and 85 °C, respectively. The purified enzyme had specific activities of 7622 and 2926 U mg-1for l-asparagine and l-glutamine, respectively, and exhibited promising thermostability at all tested temperatures from 70 to 95 °C. In addition, it displayed very high catalytic efficiency toward substrate l-asparagine. The Michaelis-Menten constant (Km), turnover number (kcat), and catalytic efficiency (kcat/Km) values for substrate l-asparagine were estimated to be 10.0 mM, 5721 s-1, and 572.1 mM-1s-1, respectively.
- Zuo, Shaohua,Xue, Dong,Zhang, Tao,Jiang, Bo,Mu, Wanmeng
-
p. 122 - 129
(2014/12/10)
-
- DIRECT CRYSTALLIZATION OF ENANTIOMERS BY HETEROGENEOUS STEREOSELECTIVE NUCLEATON ON A MEMBRANE
-
The invention concerns a procedure for the separation of optical isomers or for the production of an enantiomeric excess from a racemic mixture or from a mixture having any composition of D and L enantiomers, through direct crystallization by stereoselective nucleation on membranes functionalized with chiral detectors, or prepared starting from materials having stereoselective properties, or made by means of molecular imprinting techniques, or anyhow endowed with the ability of recognizing a specific enantiomer. The membrane carries out the double function of: i) controlling the level of supersaturation of the enantiomeric solution by means of the selective transport of solvent (or, possibly, of antisolvent), taking into account that the trans-membrane transport rate depends both on the structural parameters of the membrane and on the operation conditions; and H) promoting, on the surface of the membrane itself, the heterogeneous selective nucleation of the specific enantiomer, D or L, that preferentially interacts with the same membrane.
- -
-
Page/Page column 14-16
(2013/11/18)
-
- Biocatalytic asymmetric synthesis of unnatural amino acids through the cascade transfer of amino groups from primary amines onto keto acids
-
Flee to the hills: An unfavorable equilibrium in the amino group transfer between amino acids and keto acids catalyzed by α-transaminases was successfully overcome by coupling with a ω-transaminase reaction as an equilibrium shifter, leading to efficient asymmetric synthesis of diverse unnatural amino acids, including L-tert-leucine and D-phenylglycine. Copyright
- Park, Eul-Soo,Dong, Joo-Young,Shin, Jong-Shik
-
p. 3538 - 3542
(2014/01/06)
-
- New phenethylamine derivatives from Arenibacter nanhaiticus sp. nov. NH36A T and their antimicrobial activity
-
Five new phenethylamine (PEA) derivatives (1-5) were isolated from the strain of Arenibacter nanhaiticus sp. nov. NH36A T derived from the marine sediment of the South China Sea by bioassay-guided fractionation. Their structures were elucidated by spectro
- Chen, Yanping,Tang, Jinshan,Tang, Xixiang,Wang, Chuanxi,Lian, Yunyang,Shao, Zongze,Yao, Xinsheng,Gao, Hao
-
p. 655 - 661
(2014/01/06)
-
- Chiral octahedral complexes of CoIII as a family of asymmetric catalysts operating under phase transfer conditions
-
Stereochemically inert and positively charged chiral complexes of Co III prepared from Schiff bases derived from chiral diamines and salicylaldehydes were shown to be efficient catalysts of the asymmetric phase transfer benchmark reaction of alkylation of O'Donnell's substrate with alkyl halides. The enantiomeric purities of the reaction products were up to 92%.
- Belokon, Yuri N.,Maleev, Victor I.,North, Michael,Larionov, Vladimir A.,Savel'Yeva, Tat'Yana F.,Nijland, Aike,Nelyubina, Yuliya V.
-
p. 1951 - 1955
(2013/09/24)
-
- Characterization of d-amino acid aminotransferase from Lactobacillus salivarius
-
We searched a UniProt database of lactic acid bacteria in an effort to identify d-amino acid metabolizing enzymes other than alanine racemase. We found a d-amino acid aminotransferase (d-AAT) homologous gene (UniProt ID: Q1WRM6) in the genome of Lactobacillus salivarius. The gene was then expressed in Escherichia coli, and its product exhibited transaminase activity between d-alanine and α-ketoglutarate. This is the first characterization of a d-AAT from a lactic acid bacterium. L. salivarius d-AAT is a homodimer that uses pyridoxal-5′-phosphate (PLP) as a cofactor; it contains 0.91 molecules of PLP per subunit. Maximum activity was seen at a temperature of 60 °C and a pH of 6.0. However, the enzyme lost no activity when incubated for 30 min at 30 °C and pH 5.5 to 9.5, and retained half its activity when incubated at pH 4.5 or 11.0 under the same conditions. Double reciprocal plots of the initial velocity and d-alanine concentrations in the presence of several fixed concentrations of α-ketoglutarate gave a series of parallel lines, which is consistent with a Ping-Pong mechanism. The Km values for d-alanine and α-ketoglutarate were 1.05 and 3.78 mM, respectively. With this enzyme, d-allo-isoleucine exhibited greater relative activity than d-alanine as the amino donor, while α-ketobutylate, glyoxylate and indole-3-pyruvate were all more preferable amino acceptors than α-ketoglutarate. The substrate specificity of L. salivarius d-AAT thus differs greatly from those of the other d-AATs so far reported.
- Kobayashi, Jyumpei,Shimizu, Yasuhiro,Mutaguchi, Yuta,Doi, Katsumi,Ohshima, Toshihisa
-
-
- SEPARATING AGENT FOR CHROMATOGRAPHY
-
A separating agent for chromatography is provided that is useful for the separation of specific compounds, e.g., for the optical resolution of amino acids. This separating agent for chromatography provides a higher productivity and contains a crown ether-like cyclic structure and optically active binaphthyl. This separating agent for chromatography containing a crown ether-like cyclic structure and optically active binaphthyl is provided by introducing a substitution group for binding to carrier into a specific commercially available 1,1′-binaphthyl derivative that has substituents at the 2, 2′, 3, and 3′ positions, then introducing a crown ether-like cyclic structure, and subsequently chemically bonding the binaphthyl derivative to the carrier through the substitution group for binding to carrier.
- -
-
Paragraph 0074; 0075
(2013/08/15)
-
- Lahorenoic acids A-C, ortho-dialkyl-substituted aromatic acids from the biocontrol strain pseudomonas aurantiaca PB-St2
-
Three new aromatic acids, named lahorenoic acids A (1), B (2), and C (3), have been isolated along with the known compounds phenazine-1-carboxylic acid (4), 2- hydroxyphenazine-1-carboxylic acid (5), 2-hydroxyphenazine (6), 2,8-dihydroxyphenazine (7), cyclo-Pro-Tyr (8), cyclo-Pro- Val (9), cyclo-Pro-Met (10), and WLIP (11) and characterized from the biocontrol strain Pseudomonas aurantiaca PBSt2. The structures of these compounds were deduced by 1D and 2D NMR spectroscopic and mass spectral data interpretation. Compounds 2, 4, and 7 showed moderate antibacterial activity against mycobacteria and other Grampositive bacteria, while 4 was also found to exhibit cytotoxic and antifungal properties.
- Mehnaz, Samina,Saleem, Rahman Shah Zaib,Yameen, Basit,Pianet, Isabelle,Schnakenburg, Gregor,Pietraszkiewicz, Halina,Valeriote, Fred,Josten, Michaele,Sahl, Hans-Georg,Franzblau, Scott G.,Harald, Gross
-
p. 135 - 141
(2013/06/05)
-
- Microbial enantioselective removal of the N-benzyloxycarbonyl amino protecting group
-
In order to deprotect N-carbobenzoxy-l-aminoacids (Cbz-AA) and related compounds, a series of microorganisms was selected from soil by enrichment cultures with Cbz-l-Glu as sole nitrogen source. A lyophilized whole-cell preparation of two Arthrobacter sp. strains grown on Cbz-Glu or Cbz-Gly exhibited a high cleavage activity. The conditions of hydrolysis have been optimized and a quantitative enantioselective deprotection of several Cbz-dl-amino acids was obtained, as well as the deprotection of N-carbamoylester derivatives of several synthetic amino compounds. The preparation of Cbz-d-allylglycine and l-allylglycine in high yield and high optical purity is described as an application of this method.
- Maurs, Michele,Acher, Francine,Azerad, Robert
-
-
- New conjugates of muramyl dipeptide and nor-muramyl dipeptide linked to tuftsin and retro-tuftsin derivatives significantly influence their biological activity
-
The synthesis and biological activity of new conjugates of muramyl dipeptide (MDP) and nor-muramyl dipeptide (nor-MDP) with tuftsin and retro-tuftsin derivatives containing isopeptide bond between e-amino group of lysine and carboxyl group of simple amino
- Dzierzbicka, Krystyna,Wardowska, Anna,Rogalska, Ma?gorzata,Trzonkowski, Piotr
-
body text
p. 217 - 223
(2012/08/29)
-
- Using the same organocatalyst for asymmetric synthesis of both enantiomers of glutamic acid-derived Ni(II) complexes via 1,4-additions of achiral glycine and dehydroalanine Schiff base Ni(II) complexes
-
(S)- and (R)-BIMBOL were efficient PT catalysts of asymmetric Michael addition of prochiral Ni-PBP-Gly (1) to acrylic esters and malonic esters to Ni-PBP-Δ-Ala (2) correspondingly. The salient feature of the catalysis is opposite configurations of Glu prepared via the two paths with BIMBOL of the same configuration and a perspective novel catalytic procedure for the synthesis of Gla derivatives.
- Belokon, Yuri N.,Gugkaeva, Zalina T.,Hakobyan, Karine V.,Maleev, Victor I.,Moskalenko, Margarita A.,Khrustalev, Victor N.,Saghyan, Ashot S.,Tsaloev, Alan T.,Babievsky, Kiryl K.
-
scheme or table
p. 299 - 308
(2012/08/29)
-
- Synthesis and immunostimulating properties of novel adamant-1-yl tripeptides
-
The aim of this work was to prepare L- and D-(adamant-1-yl)-Gly-L-Ala-D- isoGln peptides in order to study their adjuvant (immunostimulating) activities. Adjuvant activity of adamant-1-yl tripeptides was tested in the mouse model using ovalbumin as an ant
- Ribic, Rosana,Habjanec, Lidija,Vranesic, Branka,Frkanec, Ruza,Tomic, Srdanka
-
experimental part
p. 777 - 788
(2012/07/27)
-
- GADD45BETA TARGETING AGENTS
-
Compounds based around tetrapeptide, tripeptide and dipeptide moeties and corresponding peptiod moeties. Related methods and pharmaceutical compositions for use in treatment of cancer, inflammatory diseases, and other disorders.
- -
-
-
- Biosynthetic origin of the 3-amino-2,5,7,8-tetrahydroxy-10-methylundecanoic acid moiety and absolute configuration of pahayokolides A and B
-
Pahayokolides A (1) and B (2) are cyclic undecapeptides that were isolated from the cyanobacterium Lyngbya sp. They contain the unusual α-hydroxy-β-amino acid 3-amino-2,5,7,8-tetrahydroxy-10- methylundecanoic acid (Athmu). The absolute configurations of the amino acids of the pahayokolides, except for the four oxygen-bearing stereocenters of Athmu, have been determined by Marphy's method. Incorporation of labeled leucine and acetate precursors into the pahayokolides has established that Athmu is derived from a leucine or α-keto isocaproic acid starter unit, which is further extended with three acetate units.
- Liu, Li,Bearden, Daniel W.,Rein, Kathleen S.
-
experimental part
p. 1535 - 1538
(2011/08/22)
-
- Structure, mechanism, and substrate profile for Sco3058: The closest bacterial homologue to human renal dipeptidase
-
Human renal dipeptidase, an enzyme associated with glutathione metabolism and the hydrolysis of β-lactams, is similar in sequence to a cluster of ~400 microbial proteins currently annotated as nonspecific dipeptidases within the amidohydrolase superfamily. The closest homologue to the human renal dipeptidase from a fully sequenced microbe is Sco3058 from Streptomyces coelicolor. Dipeptide substrates of Sco3058 were identified by screening a comprehensive series of L-Xaa-L-Xaa, L-Xaa-D-Xaa, and D-Xaa-L-Xaa dipeptide libraries. The substrate specificity profile shows that Sco3058 hydrolyzes a broad range of dipeptides with a marked preference for an L-amino acid at the N-terminus and a D-amino acid at the C-terminus. The best substrate identified was L-Arg-D-Asp (kcat/Km = 7.6 x 105 M -1 s-1). The three-dimensional structure of Sco3058 was determined in the absence and presence of the inhibitors citrate and a phosphinate mimic of L-Ala-D-Asp. The enzyme folds as a (β/α)8 barrel, and two zinc ions are bound in the active site. Site-directed mutagenesis was used to probe the importance of specific residues that have direct interactions with the substrate analogues in the active site (Asp-22, His-150, Arg-223, and Asp-320). The solvent viscosity and kinetic effects of D2O indicate that substrate binding is relatively sticky and that proton transfers do not occurr during the rate-limiting step. A bell-shaped pH-rate profile for kcat and kcat/Km indicated that one group needs to be deprotonated and a second group must be protonated for optimal turnover. Computational docking of high-energy intermediate forms of L/D-Ala-L/D-Ala to the three-dimensional structure of Sco3058 identified the structural determinants for the stereochemical preferences for substrate binding and turnover.
- Cummings, Jennifer A.,Nguyen, Tinh T.,Fedorov, Alexander A.,Kolb, Peter,Xu, Chengfu,Fedorov, Elena V.,Shoichet, Brian K.,Barondeau, David P.,Almo, Steven C.,Raushel, Frank M.
-
experimental part
p. 611 - 622
(2011/01/04)
-
- Tiglicamides A-C, cyclodepsipeptides from the marine cyanobacterium Lyngbya confervoides
-
The Floridian marine cyanobacterium Lyngbya confervoides afforded cyclodepsipeptides, termed tiglicamides A-C (1-3), along with their previously reported analogues largamides A-C (4-6), all of which possess an unusual tiglic acid moiety. Their structures
- Matthew, Susan,Paul, Valerie J.,Luesch, Hendrik
-
experimental part
p. 2058 - 2063
(2010/07/04)
-
- Facile synthesis of unsaturated pyroglutaminol derivatives
-
A novel approach to the synthesis of unsaturated pyroglutaminol derivatives was developed. Condensation of a protected serine derivative with Meldrum's acid followed by decarboxylative cyclization afforded a tetramic acid, which was then converted to a hy
- Oba, Makoto,Ito, Chihiro,Hayashi, Takahiro,Nishiyama, Kozaburo
-
scheme or table
p. 5053 - 5055
(2009/12/05)
-
- Preparation of D-amino acids by enzymatic kinetic resolution using a mutant of penicillin-G acylase from E. coli
-
We have demonstrated for the first time that d-glutamine (d-Gln) and d-glutamic acid (d-Glu) can be efficiently obtained in high ee (97% and 90%, respectively) by enzymatic kinetic resolution of d,l-Gln and d,l-Glu. This was achieved by enantioselective conversion of the l-enantiomers to their N-phenylacetyl derivatives in aqueous solution, using a mutant of penicillin-G acylase (PGA) from E. coli and phenylacetic acid methylester as the acyl donor. Kinetic modeling studies suggest that the high ee values obtained are both due to a strong enantiopreference for the l-amino acid in the deacylation step of the covalent enzyme intermediate, as well as to completeness of conversion that is transiently obtained as a result of the distinct preference of the mutant PGA for phenylacetic acid methylester over the N-phenylacetyl-l-amino acid product. For the other amino acids tested (Asn, Asp, and Ser), the highest ee values that were obtained for the remaining d-enantiomer are moderate (50-80%) because of lower enantioselectivity in the enzyme deacylation step and due to less complete conversion of the l-amino acid caused by competition for the active site between the acyl donor and the N-phenylacetyl-l-amino acid that is produced. The results demonstrate that the mutated PGA has great potential for the production of optically active D-amino acids by kinetic resolution.
- Carboni, Chiara,Kierkels, Hans G. T.,Gardossi, Lucia,Tamiola, Kamil,Janssen, Dick B.,Quaedflieg, Peter J. L. M.
-
p. 245 - 251
(2007/10/03)
-
- A small chimerically bifunctional monomeric protein: Tapes japonica lysozyme
-
The lysozyme of the marine bilave Tapes japonica (13.8 kDa) is a novel protein. The protein has 46% homology with the destabilase from medicinal leech that has isopeptidase activity. Based on these data, we confirmed hydrolysis activity of T. japonica lysozyme against three substrates: L-γ-Glu-pNA, D-γ-Glu-pNA, and ε-(γ-Glu)-L-Lys. The optimal pH of chitinase and isopeptidase activity was 5.0 and 7.0, respectively. The isopeptidase activity was inhibited with serine protease inhibitor, but the lytic and chitinase activities were not. Moreover, only isopeptidase activity is decreased by lyophilization, but lytic and chitinase activities were not. We conclude that T. japonica lysozyme expresses isopeptidase and chitinase activity at different active sites.
- Takeshita,Hashimoto,Ueda,Imoto
-
p. 1944 - 1951
(2007/10/03)
-
- 2,8'-Disubstituted-1,1'-Binaphthyls: A New Pattern in Chiral Ligands
-
The title binaphthyls 19 and 26, which are the positional isomers of 2-methoxy-2'-(diphenylphosphino)-1,1'-binaphthyl (MOP, 19) and 2-amino-2'-hydroxy-1,1'-binaphthyl (NOBIN, 26), have been synthesized by Suzuki coupling as the key step (10 + 15 -> 18), followed by functional group transformations, involving C-P and C-N bond formation (18 -> 19 and 18 -> 23). Racemic intermediate 22 was resolved by cocrystallization with N-benzylcinchonidinium chloride and the absolute configuration determined by X-ray crystallography. These novel binaphthyls are configurationally stable and, as such, potentially usable as chiral ligands in asymmetric reactions. Michael addition of the glycine-derived enolate 40 to methyl acrylate, carried out in the presence of (R)-(-)-27 as the chiral phase-transfer catalyst, afforded L-glutamic acid (S)-(+)-43 of 92% ee (after hydrolysis of the primary product).
- Vyskocil, Stepan,Meca, Ludek,Tislerova, Iva,Cisarova, Ivana,Polasek, Miroslav,Harutyunyan, Syuzanna R.,Belokon, Yuri N.,Stead, Russel M. J.,Farrugia, Louis,Lockhart, Stephen C.,Mitchell, William L.,Kocovsky, Pavel
-
p. 4633 - 4648
(2007/10/03)
-
- Retention and selectivity of teicoplanin stationary phases after copper complexation and isotopic exchange
-
Teicoplanin is a macrocyclic glycopeptide that is highly effective as a chiral selector for LC enantiomeric separations. Two possible interaction paths were investigated and related to solute retention and selectivity: (1) interactions with the only teicoplanin amine group and (2) role of hydrogen bonding interactions. Mobile phases containing 0.5 and 5 mM copper ions were used to try to block the amine group. In the presence of copper ions, it was found that the teicoplanin stationary phase has a decreased ability to separate most underivatized racemic amino acids. However, it maintained its ability to separate enantiomers that were not α - amino acids. It is established that there is little copper - teicoplanin complex formation. The effect of Cu2+ on the enantioseparation of some α - amino acids appears to be due to the fact that these solutes are good bidentate ligands and form complexes with copper ions in the mobile phase. Isotopic exchange with deuterium oxide was performed using acetonitrile - heavy water mobile phases. It was found that the retention times of all amino acids were lower with deuterated mobile phases. The retention times of polar or apolar molecules without amine groups were higher with deuterated mobiles phases. In all cases, the enantio-selectivity factors were unaffected by the deuterium exchange. It is proposed that the electrostatic interactions are decreased in the deuterated mobile phases and the solute-accessible stationary-phase volume is somewhat swollen by deuterium oxide. The balance of these effects is a decrease in the amino acid retention times and an increase in the apolar solute retention time. The enantio-selectivity factors of all of the molecules remain unchanged because all of the interactions are changed equally. We propose a new global quality criterion (the E factor) for comparing and evaluating enantiomeric separations.
- Berthod,Valleix,Tizon,Leonce,Caussignac,Armstrong
-
p. 5499 - 5508
(2007/10/03)
-
- Specific host-guest interactions in a protein-based artificial transaminase
-
Artificial enzymes can be created by covalent attachment of a catalytic active group to a protein scaffold. Recently, we assembled an artificial transaminase by conjugation of intestinal fatty acid binding protein (IFABP) with a pyridoxamine derivative via a disulfide bond; the resulting constract catalyzed a transamination reaction 200-fold faster than free pyridoxamine. To identify the origin of this increased catalytic efficiency computer modeling was first used to identify two putative residues, Y14 and R126, that were in close proximity to the γ-carboxylate group of the substrate, α-ketoglutartate. These positions were mutated to phenylalanine and methionine, respectively, and used to prepare semisynthetic transaminases by conjugation to pyridoxamine (Px) or an N-methylated derivative (Px). Kinetic analysis of the resulting constructs showed that the R126 mutation reduced substrate affinity 3- to 6-fold while the additional Y14F mutation had a negligible effect. These results are consistent with a model for substrate recognition that involves an electrostatic interaction between the cationic guanidinium group of R126 and the anionic carboxylate from the substrate. Interestingly, one of the conjugates that contains an N-methylated pyridoxamine catalyzes a transamination reaction with a kcat we have thus far obtained and is 34-fold greater than that for the free cofactor in the absence of the protein. Copyright
- Haering, Dietmar,Distefano, Mark D
-
p. 2461 - 2466
(2007/10/03)
-
- Antiherpes virus compounds and methods for their preparation and use
-
This invention relates to methods for inhibiting herpes replication and for treating herpes infection in a mammal by inhibiting the herpes helicase-primase enzyme complex. This invention also relates to thiazolyphenyl derivatives that inhibit the herpes helicase-primase and to pharmaceutical compositions comprising the thiazolylphenyl derivatives, to methods of using and methods of producing the thiazolylphenyl derivatives
- -
-
-
- Anti-herpesvirus compounds and methods for identifying, making and using same
-
This invention relates to methods for inhibiting herpes replication and for treating herpes infection in a mammal by inhibiting the herpes helicase-primase enzyme complex. This invention also relates to thiazolyphenyl derivatives that inhibit the herpes helicase-primase and to pharmaceutical compositions comprising the thiazolylphenyl derivatives, to methods of using and methods of producing the thiazolylphenyl derivatives.
- -
-
-
- Compounds for and methods of inhibiting matrix metalloproteinases
-
The present invention relates to compounds of Formula I that inhibit matrix metalloproteinases and to a method of inhibiting matrix metalloproteinases using the compounds More particularly, the present invention relates to a method of treating diseases in which matrix metalloproteinases are involved such as multiple sclerosis, atherosclerotic plaque rupture, restenosis, aortic aneurysm, heart failure, periodontal disease, corneal ulceration, burns, decubital ulcers, chronic ulcers or wounds, cancer metastasis, tumor angiogenesis, osteoporosis, rheumatoid or osteoarthritis, renal disease, left ventricular dilatation, or other autoimmune or inflammatory diseases dependent upon tissue invasion by leukocytes.
- -
-
-
- Synthesis of a cationic pyridoxamine conjugation reagent and application to the mechanistic analysis of an artificial transaminase
-
An N-methylated, cationic pyridoxamine conjugation reagent was synthesized and tethered via a disulfide bond to a cysteine residue inside the cavity of intestinal fatty acid binding protein. The conjugate was characterized and the kinetic parameters compared to its nonmethylated pyridoxamine analogue. Kinetic isotope effects were used for further mechanistic analysis. Taken together, these experiments suggest that a step distinct from deprotonation of the ketimine in the pyridoxamine to pyridoxal reaction is what limits the rate of the artificial transaminase IFABP-Px. However, the internal energetics of reactions catalyzed by the conjugate containing the N-methylated cofactor appear to be different suggesting that the MPx reagent will be useful in future experiments designed to alter the catalytic properties of semisynthetic transaminases. (C) 2000 Elsevier Science Ltd.
- Kuang, Hao,Haering, Dietmar,Qi, Dongfeng,Mazhary, Aram,Distefano, Mark D.
-
p. 2091 - 2095
(2007/10/03)
-
- Production of D-glutamate from L-glutamate with glutamate racemase and L-glutamate oxidase
-
We studied production of D-glutamate from L-glutamate using a bioreactor consisting of two columns of sequentially connected immobilized glutamate racemase (EC 5.1.1.3, from Bacillus subtilis IFO 3336) and L-glutamate oxidase (EC 1.4.3.11, from Streptomyces sp. X119-6): L-glutamate was racemized by the glutamate racemase column, and then L-glutamate was oxidized by the L-glutamate oxidase column. Consequently only D-glutamate remained, and was easily separated from the α-ketoglutarate formed by anion-exchange chromatography. Both enzymes were highly stabilized by immobilization. The pH and temperature optima of immobilized glutamate racemase (pH 8, 40°C) were similar to those of immobilized L-glutamate oxidase (pH 7, 50°C). Accordingly, we connected the two columns tandemly to do both enzyme reactions under the same conditions. Actually 4.5 μmol of D-glutamate was produced and isolated from 10 μmol of L-glutamate, about 90% of the theoretical yield.
- Oikawa, Tadao,Watanabe, Mayumi,Makiura, Hidemi,Kusakabe, Hitoshi,Yamade, Kazuhiro,Soda, Kenji
-
p. 2168 - 2173
(2007/10/03)
-
- Fatty acid analogs and prodrugs
-
Novel derivatives of fatty acid analogs that have from one to three heteroatoms in the fatty acid moiety which can be oxygen, sulfur or nitrogen, are disclosed in which the carboxy-terminus has been modified to form various amides, esters, ketones, alcohols, alcohol esters and nitrites thereof. These compounds are useful as substrates for N-myristoyltransferase (NMT) and/or its acyl coenzyme, and as anti-viral and anti-fungal agents or pro-drugs of such agents. Illustrative of the disclosed compounds are fatty acid amino acid analogs of the structure STR1 in which x is the ethyl or t-butyl ester of an amino acid such as Gly, L-Ala, L-Ile, L-Phe, L-Trp, L-Thr or an amide such as NHCH2 C6 H5 or NH(CH2)2 C6 H5.
- -
-
-
- Highly diastereoselective monoalkylation and Michael addition of N- (diphenylmethylene)glycinesultam under solid-liquid phase-transfer catalysis conditions using potassium carbonate as base
-
Treatment of a sultam-derived N-(diphenylmethylene)glycinate equivalent 1 with activated (allylic and propargylic) organic bromides and with Michael acceptors under solid-liquid phase-transfer catalysis conditions, using potassium carbonate as base, affords the monoalkylated compounds with high diastereoselectivity (>97% d.e.).
- Lopez, Anna,Pleixats, Roser
-
p. 1967 - 1977
(2007/10/03)
-
- Fatty acid analogs and prodrugs
-
Novel derivatives of fatty acid analogs that have from one to three heteroatoms in the fatty acid moiety which can be oxygen, sulfur or nitrogen, are disclosed in which the carboxy-terminus has been modified to form various amides, esters, ketones, alcohols, alcohol esters and nitriles thereof. These compounds are useful as substrates for N-myristoyltransferase (NMT) and/or its acyl coenzyme, and as anti-viral and anti-fungal agents or pro-drugs of such agents. Illustrative of the disclosed compounds are fatty acid amino acid analogs of the structure STR1 in which X is the ethyl or t-butyl ester of an amino acid such as Gly, L--Ala, L--Ile, L--Phe, L--Trp, L--Thr or an amide such as NHCH2 C6 H5 or NH(CH2)2 C6 H5,
- -
-
-
- Modulation of the rate, enantioselectivity, and substrate specificity of semisynthetic transaminases based on lipid binding proteins using site directed mutagenesis
-
Fatty acid binding proteins are a class of small 15 kDa proteins with a simple architecture that forms a large solvent sequestered cavity. In previous work, we demonstrated that reductive amination reactions could be performed in this cavity by covalent attachment of a pyridoxamine cofactor to the protein. Here, we report the results of experiments in which the position of pyridoxamine attachment has been varied by site directed mutagenesis. The conjugate IFABP-PX60 reacts at least 9.4-fold more rapidly than our original conjugate ALBP-PX, while IFABP-PX72 inverts the enantioselectivity of reactions (compared to ALBP-PX) and IFABP-PX104 displays very selective substrate specificity. These results indicate that site-directed mutagenesis can be used to tune the rate, enantioselectivity, and substrate specificity of semisynthetic transaminases based on fatty acid binding proteins.
- Kuang, Hao,Davies, Ronald R.,Distefano, Mark D.
-
p. 2055 - 2060
(2007/10/03)
-
- 2-SUBSTITUTED 3-(4-AMIDINOPHENYL)PROPIONIC ACID DERIVATIVES
-
2-Substituted 3-(4-amidinophenyl)propionic acid derivatives of the formula STR1 in which A, Ar and B have the meanings stated in the description, and the preparation thereof are described. The compounds are suitable for controlling diseases.
- -
-
-
- Enantioselective reductive amination of α-keto acids to α-amino acids by a pyridoxamine cofactor in a protein cavity
-
Adipocyte lipid binding protein (ALBP) is a small 131 residue protein with a simple architecture that consists of two orthogonal planes of β-sheet secondary structure. This protein binds a variety of fatty acids in a large cavity formed between the two sheets such that the bound ligands are completely enclosed within the protein. In this paper, the synthesis of an ALBP conjugate (ALBP-PX) containing a pyridoxamine cofactor attached to a thiol within the protein interior is described. The conjugate was characterized by mass spectrometry, UV/vis spectroscopy, and gel filtration chromatography. ALBP-PX reductively aminates a number of alkyl, aryl, and side chain functionalized α-keto acids to α-amino acids with enantioselectivities as high as 94% ee.
- Kuang, Hao,Brown, Matthew L.,Davies, Ronald R.,Young, Eva C.,Distefano, Mark D.
-
p. 10702 - 10706
(2007/10/03)
-
- Asymmetric Catalysis by Vitamin B12: The Isomerization of Achiral Aziridines to Optically Active Allylic Amines
-
Achiral N-acylaziridines are isomerized to optically active N-acyl-allylamines in ee's of up to 95percent by catalytic amounts of cob(I)alamin in MeOH.
- Zhang, Zhong da,Scheffold, Rolf
-
p. 2602 - 2615
(2007/10/02)
-
- Effect of the Side Chain on the Racemization of Amino Acids in Aqueous Solution
-
The rate of racemization of 13 amino acids possessing hydroxy, carboxy, alkoxy, carboalkoxy, alkyl, aryl, and thioether side chains were compared.Reaction conditions were identical for all amino acids studied.Gas chromatography was used to determine the percent of D isomer present.Hydroxy amino acids racemized most rapidly, but conversion to an ether function reduced the rate considerably.The increased racemization rate of methionine (R = CH2CH2SCH3) over Ala (R = CH3) has been attributed to orbital overlap from the sulfur.Asp racemized faster than Glu, α-aminoadipic acid, and pyroglutamic acid. β- and γ-monomethyl esters of aspartic and glutamic acids, respectively, racemized only slightly faster than the corresponding free acids.The slight increase in rate appears attributable to a solvent change brought on by ester hydrolysis.Under the reaction conditions, pH 8 and 140 deg C, hydrolysis of the esters competed favorably with racemization at the methine carbon.The relatively lower racemization rate observed in the case of Glu compared with Asp resulted from the slow formation of pyroglutamic acid.Pyroglutamic acid racemized at a considerably slower rate than acidic amino acids.The differences in the racemization rates with changes in the R group are discussed in terms of several factors, including intramolecular reactions, direct field effects, orbital overlap, and solvation effects, as well as inductive, resonance, and steric factors.
- Smith, Grant Gill,Reddy, G. Vanita
-
p. 4529 - 4535
(2007/10/02)
-
- Method of making a diastereomeric mixture containing two diastereomeric N-acyl-amino acid esters
-
In the process of hydrocarboxylating an α-enamide with CO and an organic hydroxyl compound to produce a N-acyl-α-amino acid ester, the improvement comprising using as the organic hydroxyl compound reactant, an organic hydroxyl compound which has a chiral center that is essentially all L or D, thereby producing a reaction mixture having essentially no enantiomeric pairs and containing diastereomeric N-acyl-α-amino acid esters having two chiral centers.
- -
-
-
- ASYMMERTIC SYNTHESIS OF Β-SUBSTITUTED α-AMINO ACIDS VIA A CHIRAL Ni(II) COMPLEX OF DEHYDROALANINE
-
An efficient approach to the asymmetric synthesis of β-substituted (S)-alanines is describen.The chiral Ni(II) complex of a Schiff base derived from (S)-o-N-(N-benzylpropyl)aminobenzophenone (BBP) and glycine was treated with formaldehyde and sodium methoxide to give a corresponding (R)-serine complex which, in turn, was converted to the chiral Ni(II) dehydroalanine complex.Michael type base catalyzed addition of nucleophiles (including MeOH, Me2NH, PhCH2NH2, imidazole, PhSH, PhCH2SH,, malonic ester and benzylmagnesium chloride) produced a mixture of diastereoisomeric complexes with a 70-90percent excess of S,S (or L,L) isomers over the S,R (or L,D) ones.The cleavage of pure diastereoisomers with aqueous HCl gave, in good yields, β-substituted (S) (or L)-alanines and regenerated the chiral auxiliary (BBP).
- Belokon, , Yuri N.,Sagyan, Ashot S.,Djamgaryan, Silva M.,Bakhmutov, Vladimir I.,Belikov, Vasili M.
-
p. 5507 - 5514
(2007/10/02)
-