- Biochemical characterization of an extremely thermostable l-asparaginase from Thermococcus gammatolerans EJ3
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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
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- Structure, mechanism, and substrate profile for Sco3058: The closest bacterial homologue to human renal dipeptidase
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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.
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- Propagation of biochirality: Crossovers and nonclassical crystallization kinetics of aspartic acid in water
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All experimental procedures discussed could be treated as a screening tool for probing the existence of molecular association among the chiral molecules and the solvent system. The molecular association phases of a racemic conglomerate solution (CS) and a
- Lee, Tu,Lin, Yu Kun,Tsai, Ya Chung,Lee, Hung Lin
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- AN AGE DETERMINATION OF AN ANCIENT BURIAL MOUND MAN BY APPARENT RACEMIZATION REACTION OF ASPERTIC ACID IN TOOTH DENTIN
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An age of a man from an ancient burial mound dated to the seventh century was estimated to be about 50 years old, using an apparent racemizatiopn phenomenon of aspartic acid found from the tooth dentin.For this estimate, the D/L ratios of modern teeth and
- Shimoyama, Akira,Harada, Kaoru
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- Structural and functional analysis of pantocin A: An antibiotic from Pantoea agglomerans discovered by heterologous expression of cloned genes
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Small-molecule chemistry and biochemical techniques have been used to determine the structure and mode of function of pantocin A (see structure), a naturally occurring antibiotic. Pantocin A functions as an inhibitor of histidine biosynthesis, as shown by its ability to inhibit the action of L-histidinol phosphate aminotransferase, which converts imidazole acetol phosphate to L-histidinol phosphate in Escherichia coli.
- Jin, Mi,Liu, Liang,Wright, Sandra A. I.,Beer, Steven V.,Clardy, Jon
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- Evidence of the hypsithermal verified using the racemization rate constant of amino acids: An estimation of paleo-ground temperatures
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The kinetics of a racemization reaction for aspartic acid in boreal terrestrial sediment core samples was investigated in detail to determine the rate constant (kASP) and the difference of the paleo-ground temperatures. The Arrhenius plot betwe
- Takano, Yoshinori,Kudo, Junya,Kaneko, Takeo,Kobayashi, Kensei,Ishikawa, Yoji,Marumo, Katsumi
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- Optical Resolution of Aspartic Acid by Using Copper Complexes of Optically Active Amino Acids
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DL-Aspartic acid was resolved with high optical purity in the presence of an optically active amino acid copper complex.The mechanism of the optical resolution was explained by the competitive inhibition of crystallization.
- Harada, Kaoru,Fujii, Noriko
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- Racemization of the aspartic acid residue of amyloid-β peptide by a radical reaction
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Human amyloid-β peptide 1-42 (Aβ) was subjected to a radical reaction by using ascorbic acid and CuCl2. The percentage of D-aspartic acid (D-Asp) after 24 h had increased to 6.69 ± 0.09%, this being comparable with the reported D-Asp concentration of purified core amyloids in Alzheimer's disease patients. This racemization was significantly inhibited by radical scavengers. L-Alanine was also racemized during the same reaction.
- Tambo, Koharu,Yamaguchi, Tomomi,Kobayashi, Keiko,Terauchi, Eri,Ichi, Ikuyo,Kojo, Shosuke
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- Switchable Chiral Selection of Aspartic Acids by Dynamic States of Brushite
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We herein show the chiral recognition and separation of aspartic acid (Asp) enantiomers by achiral brushite due to the asymmetries of their dynamical steps in its nonequilibrium states. Growing brushite has a higher adsorption affinity to d-Asp, while l-A
- Jiang, Wenge,Pan, Haihua,Zhang, Zhisen,Qiu, S. Roger,Kim, J. Dongun,Xu, Xurong,Tang, Ruikang
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- Immobilization of L-aspartate oxidase from Sulfolobus tokodaii as a biocatalyst for resolution of aspartate solutions
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L-Aspartate oxidase from the thermophilic archaebacterium Sulfolobus tokodaii (StLASPO) catalyzes the stereoselective oxidative deamination of L-aspartate to yield oxaloacetate, ammonia and hydrogen peroxide. The recombinant flavoenzyme shows distinctive
- D'Arrigo, Paola,Allegretti, Chiara,Fiorati, Andrea,Piubelli, Luciano,Rosini, Elena,Tessaro, Davide,Valentino, Mattia,Pollegioni, Loredano
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- Noncovalently Functionalized Commodity Polymers as Tailor-Made Additives for Stereoselective Crystallization
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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
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supporting information
p. 20243 - 20248
(2021/08/09)
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- Structure-guided engineering of: Pseudomonas dacunhae l-aspartate β-decarboxylase for l-homophenylalanine synthesis
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Structure-guided engineering of Pseudomonas dacunhael-aspartate β-decarboxylase (AspBDC) resulted in a double mutant (R37A/T382G) with remarkable 15400-fold improvement in specific activity reaching 216 mU mg-1, towards the target substrate 3(R)-benzyl-l-aspartate. A novel strategy for enzymatic synthesis of l-homophenylalanine was developed by using the variant as a biocatalyst affording 75% product yield within 12 h. Our results underscore the potential of engineered AspBDC for the biocatalytic synthesis of pharmaceutically relevant and value added unnatural l-amino acids.
- Zhang, Min,Hu, Pengfei,Zheng, Yu-Cong,Zeng, Bu-Bing,Chen, Qi,Zhang, Zhi-Jun,Xu, Jian-He
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p. 13876 - 13879
(2020/11/18)
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- Unique polyhalogenated peptides from the marine sponge Ircinia sp.
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Two new bromopyrrole peptides, haloirciniamide A (1) and seribunamide A (2), have been isolated from an Indonesian marine sponge of the genus Ircinia collected in the Thousand Islands (Indonesia). The planar structure of both compounds was assigned on the basis of extensive 1D and 2D NMR spectroscopy and mass spectrometry. The absolute configuration of the amino acid residues in 1 and 2 was determined by the application of Marfey's method. Compound 1 is the first dibromopyrrole cyclopeptide having a chlorohistidine ring, while compound 2 is a rare peptide possessing a tribromopyrrole ring. Both compounds failed to show significant cytotoxicity against four human tumor cell lines, and neither compound was able to inhibit the enzyme topoisomerase I or impair the interaction between programmed cell death protein PD1 and its ligand, PDL1.
- Fernández, Rogelio,Bayu, Asep,Hadi, Tri Aryono,Bueno, Santiago,Pérez, Marta,Cuevas, Carmen,Putra, Masteria Yunovilsa
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- Preparation and characterization of a new open-tubular capillary column for enantioseparation by capillary electrochromatography
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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
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p. 283 - 292
(2019/02/05)
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- Covalent Organic Frameworks with Chirality Enriched by Biomolecules for Efficient Chiral Separation
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The separation of racemic compounds is important in many fields, such as pharmacology and biology. Taking advantage of the intrinsically strong chiral environment and specific interactions featured by biomolecules, here we contribute a general strategy is developed to enrich chirality into covalent organic frameworks (COFs) by covalently immobilizing a series of biomolecules (amino acids, peptides, enzymes) into achiral COFs. Inheriting the strong chirality and specific interactions from the immobilized biomolecules, the afforded biomolecules?COFs serve as versatile and highly efficient chiral stationary phases towards various racemates in both normal and reverse phase of high-performance liquid chromatography (HPLC). The different interactions between enzyme secondary structure and racemates were revealed by surface-enhanced Raman scattering studies, accounting for the observed chiral separation capacity of enzymes?COFs.
- Zhang, Sainan,Zheng, Yunlong,An, Hongde,Aguila, Briana,Yang, Cheng-Xiong,Dong, Yueyue,Xie, Wei,Cheng, Peng,Zhang, Zhenjie,Chen, Yao,Ma, Shengqian
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supporting information
p. 16754 - 16759
(2018/11/27)
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- Chromatographic Resolution of α-Amino Acids by (R)-(3,3'-Halogen Substituted-1,1'-binaphthyl)-20-crown-6 Stationary Phase in HPLC
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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
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supporting information
p. 1037 - 1042
(2017/07/25)
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- D-asparaginic acid preparation method
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The invention discloses a D-asparaginic acid preparation method. The configuration inversion technology is adopted, and the preparation method comprises the steps that L-dimethyl malate-2-besilate can be formed by generating L-dimethyl malate through L-malic acid and then making the L-dimethyl malate react with benzene sulfonyl chloride, then the L-dimethyl malate-2-besilate is made to react with phthalimide potassium, and benzenesulfonic acid serves as a good removal agent, so that D- dimethyl aspartate-2-phthalimide is formed, hydrolysis is conducted under the alkaline condition, D-disodium aspartate is generated, after passing through cation exchange resin, effluent is subjected to concentration, and ethyl alcohol with the concentration being 95% is added for crystallization, so that D-asparaginic acid is obtained. By means of the method, neither high temperature nor high pressure is needed, resolution is not needed, environmental pollution is not caused, and the yield can reach 75% and above.
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Paragraph 0026
(2016/11/28)
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- 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
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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
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p. 1815 - 1838
(2014/06/09)
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- SEPARATING AGENT AND MANUFACTURING METHOD THEREOF
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An embodiment of the present invention is a separating agent wherein a group represented by a chemical formula of: or a group represented by a chemical formula of: is introduced on a surface thereof.
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Paragraph 0067; 0068; 0069; 0070; 0071; 0072; 0103; 0104
(2015/01/07)
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- Characterization of d-amino acid aminotransferase from Lactobacillus salivarius
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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
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- SEPARATING AGENT FOR CHROMATOGRAPHY
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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.
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Paragraph 0074; 0075
(2013/08/15)
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- GADD45BETA TARGETING AGENTS
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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.
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- JBIR-78 and JBIR-95: Phenylacetylated peptides isolated from Kibdelosporangium sp. AK-AA56
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The search for metabolites of Kibdelosporangium sp. AK-AA56 resulted in the discovery of novel N-phenylacetylated peptides, JBIR-78 (1) and JBIR-95 (2). Compounds 1 and 2 were established to be N-phenylacetylated heptapeptides by extensive NMR and HRESIMS analyses. The absolute configuration of the standard amino acids including a cysteic acid moiety was determined using Marfey's method on the acid hydrolysates of 1 and 2. The relative and absolute configurations of a nonstandard amino acid, β-hydroxyleucine, were elucidated using the J-based and modified Mosher's methods, respectively. In an antimicrobial test, 1 showed antibacterial activity against Micrococcus luteus.
- Izumikawa, Miho,Takagi, Motoki,Shin-Ya, Kazuo
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experimental part
p. 280 - 284
(2012/05/19)
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- Chiral separation of aspartic acid by thin-layer chromatography
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In this study, chiral separation of D/L-aspartic acid was achieved by thin layer chromatography using L-arginine as a chiral separator using the mobile phase as butanol:glacial acetic acid:water (70:10:20) and the visualizing agent is ninhydrin and butano
- Katiyar, Prashant K.,Wala, Ravi Kabra
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experimental part
p. 4945 - 4946
(2010/12/24)
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- Solution-phase racemization in the presence of an enantiopure solid phase
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Solution-phase racemization drives the evolution of single chirality in the solid phase by the "chiral amnesia" process first described by Viedma. The current investigations lay the basis for a better understanding of the mechanism of the solid-phase dera
- Viedma, Cristobal,Verkuijl, Bastiaan J. V.,Ortiz, Jose E.,De Torres, Trinidad,Kellogg, Richard M.,Blackmond, Donna G.
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experimental part
p. 4932 - 4937
(2010/08/03)
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- Preparation of D-amino acids by enzymatic kinetic resolution using a mutant of penicillin-G acylase from E. coli
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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.
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p. 245 - 251
(2007/10/03)
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- Analysis of underivatized amino acids and their D/L-enantiomers by sheathless capillary electrophoresis/electrospray ionization-mass spectrometry
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Capillary electrophoresis/electrospray ionization-mass spectrometry (CE/ESI-MS) was applied to the analysis of underivatized amino acids and the separation of their D/L-enantiomers. Under full-scan mode, all standard protein amino acids were separated and detected at low-femtomole levels using a 130-cm-long, 20-μm-i.d., 150-μm-o.d. underivatized fused-silica capillary with 1 M formic acid as the background electrolyte. The CE/ESI-MS technique was also applied to the separation of L-arginine from L-canavanine (a close analogue of arginine where the terminal methylene linked to the guanidine group of arginine is replaced by an oxygen atom) in a complex mixture containing all standard protein amino acids. The utility of CE/ESI-MS in the analysis of real-world samples was demonstrated by the identification of two metabolic diseases (PKU and tyrosinemia) through blood analysis with minimal sample preparation. In addition, the on-line separation of 11 underivatized L-amino acids from their D-enantiomers was achieved by using a 30 mM solution of (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid as the background electrolyte.
- Schultz, Casey L.,Moini, Mehdi
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p. 1508 - 1513
(2007/10/03)
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- Serine octamer reactions: Indicators of prebiotic relevance
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The earliest molecule of life? Chirally selective reactions relevant to the origin of homochiral life are undergone by serine. Chiral exchange between serine, glyceraldehyde, and glucose occurs, favoring the enantiomers (L-serine, D-sugars) present in modern living systems (see picture).
- Takats, Zoltan,Nanita, Sergio C.,Cooks, R. Graham
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p. 3521 - 3523
(2007/10/03)
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- Retention and selectivity of teicoplanin stationary phases after copper complexation and isotopic exchange
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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
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p. 5499 - 5508
(2007/10/03)
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- Compounds for and methods of inhibiting matrix metalloproteinases
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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.
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- Pholipeptin, a novel cyclic lipoundecapeptide from Pseudomonas fluorescens
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An inhibitor of phosphatidylinositol-specific phospholipase C (PI-PLC), pholipeptin (1), was purified from the culture broth of Pseudomonas sp. by solvent extraction and column chromatography. Acid hydrolysis of 1 gave Leu, Ile, Ser, Thr, and Asp moieties
- Ui, Hideaki,Miyake, Toshiaki,Iinuma, Hironobu,Imoto, Masaya,Naganawa, Hiroshi,Hattori, Seiko,Hamada, Masa,Takeuchi, Tomio,Umezawa, Sumio,Umezawa, Kazuo
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p. 103 - 108
(2007/10/03)
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- Asymmetric Alkylation of 8-Phenylmenthyl N-glycinate Enolates. Synthesis of D- and L-α-Amino Acids from a Single Chiral Precursor
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The herein described studies on the enolization and subsequent alkylation of the acyclic glycine title ester evidence the involvement of the kinetics of the alkylation step on the stereochemical outcome of the overall process, apart from that of the deprotonation sequence itself.Careful choice of reaction conditions allow for the selective obtention of α-amino acids either of the L- or the D-series without the need of changing the chiral inducer: deprotonation with LDA or t-BuLi followed by reaction with alkyl triflates gives rise to the 2R- α-amino acids, whereas the 2S isomers can be obtained by deprotonation with KO-t-Bu followed by reaction with alkyl halides.
- Alvarez-Ibarra, Carlos,Csaky, Aurelio G.,Maroto, Raquel,Quiroga, M. Luz
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p. 7934 - 7940
(2007/10/03)
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- ASYMMETRIC SYNTHESIS OF ASPARTIC AND α-METHYLASPARTIC ACIDS VIA Ni(II) COMPLEXES WITH SCHIFF BASES OF GLYCINE AND ALANINE AND CHIRAL CARBONYL-CONTAINING REAGENTS
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We propose a method for the synthesis of aspartic and α-methylaspartic acids by alkylation with ethyl bromoacetate of the α-carbon atom of the amino acid moiety in Ni(II) complexes of Schiff bases of glycine with (S)-2-benzophenone and alanine with (S)-2-benzaldehyde, respectively.Attempts to synthesize α-methylaspartic acid by oxidative cleavage of the C=C bond to a COOH group in the complex of the Schiff base of α-allylalanine with (S)-2-benzophenone were unsuccessful.
- Belokon, Yu. N.,Tararov, V. I.,Maleev, V. I.,Motsishkite, S. M.,Vitt, S. V.,et al.
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p. 1361 - 1365
(2007/10/02)
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- Method of making a diastereomeric mixture containing two diastereomeric N-acyl-amino acid esters
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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.
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- Effect of the Side Chain on the Racemization of Amino Acids in Aqueous Solution
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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
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p. 4529 - 4535
(2007/10/02)
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- Synthesis of a Chiral Nickel(II) Complex of an Electrophilic Glycinate, and its Use for Asymmetric Preparation of α-Amino Acids
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A chiral NiII complex of a Schiff's base derived from (S)-o-benzophenone and α-bromoglycine has been obtained and its stereoselective reaction with nucleophiles studied; the synthesis of aspartic acid with 80percent optical purity is described.
- Belokon', Yuri N.,Popkov, Aleksander N.,Chernoglazova, Nina I.,Saporovskaya, Marina B.,Bakhmutov, Vladimir I.,Belikov, Vasili M.
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p. 1336 - 1338
(2007/10/02)
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- Use of LRH and LRH agonists
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The use of LRH and LRH agonists as contraceptives in the planetal mammal is disclosed.
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