- Structures and antitumor activities of ten new and twenty known surfactins from the deep-sea bacterium Limimaricola sp. SCSIO 53532
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Surfactins are natural biosurfactants with myriad potential applications in the areas of healthcare and environment. However, surfactins were almost exclusively produced by the bacterium Bacillus species in previous reported literatures, together with difficulty in isolating pure monomer, which resulted in making extensive effort to remove duplication and little discovery of new surfactins in recent years. In the present study, the result of Molecular Networking indicated that Limimaricola sp. SCSIO 53532 might well be a potential resource for surfacin-like compounds based on OSMAC strategy. To search for new surfactins with significant biological activity, further study was undertaken on the strain. As a result, ten new surfactins (1–10), along with twenty known surfactins (11–30), were isolated from the ethyl acetate extract of SCSIO 53532. Their chemical structures were established by detailed 1D and 2D NMR spectroscopy, HRESIMS data, secondary ion mass spectrometry (MS/MS) analysis, and chemical degradation (Marfey's method) analysis. Cytotoxic activities of twenty-seven compounds against five human tumor cell lines were tested, and five compounds showed significant antitumor activities with IC50 values less than 10 μM. Furtherly, analysis of structure–activity relationships revealed that the branch of side chain, the esterification of Glu or Asp residue, and the amino acid residue of position 7 possessed a great influence on antitumor activity.
- Chen, Min,Chen, Rouwen,Ding, Wenping,Li, Yanqun,Tian, Xinpeng,Yin, Hao,Zhang, Si
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- Mechanically Strong Heterogeneous Catalysts via Immobilization of Powderous Catalysts to Porous Plastic Tablets
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Main observation and conclusion: We describe a practical and general protocol for immobilization of heterogeneous catalysts to mechanically robust porous ultra-high molecular weight polyethylene tablets using inter-facial Lifshitz-van der Waals Interactions. Diverse types of powderous catalysts, including Cu, Pd/C, Pd/Al2O3, Pt/C, and Rh/C have been immobilized successfully. The immobilized catalysts are mechanistically robust towards stirring in solutions, and they worked well in diverse synthetic reactions. The immobilized catalyst tablets are easy to handle and reused. Moreover, the metal leaching of immobilized catalysts was reduced significantly.
- Li, Tingting,Xu, Bo
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supporting information
p. 2673 - 2678
(2021/08/03)
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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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- Leveraging Peptaibol Biosynthetic Promiscuity for Next-Generation Antiplasmodial Therapeutics
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Malaria remains a worldwide threat, afflicting over 200 million people each year. The emergence of drug resistance against existing therapeutics threatens to destabilize global efforts aimed at controlling Plasmodium spp. parasites, which is expected to leave vast portions of humanity unprotected against the disease. To address this need, systematic testing of a fungal natural product extract library assembled through the University of Oklahoma Citizen Science Soil Collection Program has generated an initial set of bioactive extracts that exhibit potent antiplasmodial activity (EC50 25 μM, selectivity index > 250). The unique chemodiversity afforded by these fungal isolates serves to unlock new opportunities for translating peptaibols into a bioactive scaffold worthy of further development.
- Lee, Jin Woo,Collins, Jennifer E.,Wendt, Karen L.,Chakrabarti, Debopam,Cichewicz, Robert H.
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supporting information
p. 503 - 517
(2021/03/01)
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- Method for photolysis of amido bonds
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The invention discloses a method for photo-splitting amido bonds, wherein the method is mild in reaction condition and can realize splitting of amido bonds by using illumination. The method for photo-splitting the amido bonds comprises the following steps: reacting 2,4-dinitrofluorobenzene with an amino group of a substance which contains alpha amino acid at the tail end and is shown as a structural formula I to generate a compound 1 represented by a structural formula II; and under light irradiation, carrying out amido bond cleavage reaction on the compound 1, wherein R1 is a side chain group of alpha-amino acid, and R2 is aryl, aliphatic hydrocarbon, -CH(R)-COOH or polypeptide.
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Paragraph 0046; 0048-0049; 0114-0117
(2021/06/26)
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- Powerful Steroid-Based Chiral Selector for High-Throughput Enantiomeric Separation of α-Amino Acids Utilizing Ion Mobility-Mass Spectrometry
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Stereospecific recognition of amino acids (AAs) plays a crucial role in chiral biomarker-based diagnosis and prognosis. Separation of AA enantiomers is a long and tedious task due to the requirement of AA derivatization prior to the chromatographic or electrophoretic steps which are also time-consuming. Here, a mass-tagged chiral selector named [d0]/[d5]-estradiol-3-benzoate-17β-chloroformate ([d0]/[d5]-17β-EBC) with high reactivity and good enantiomeric resolution in regard to AAs was developed. After a quick and easy chemical derivatization step of AAs using 17β-EBC as the single chiral selector before ion mobility-mass spectrometry analysis, good enantiomer separation was achieved for 19 chiral proteinogenic AAs in a single analytical run (~2 s). A linear calibration curve of enantiomeric excess was also established using [d0]/[d5]-17β-EBC. It was demonstrated to be capable of determining enantiomeric ratios down to 0.5% in the nanomolar range. 17β-EBC was successfully applied to investigate the absolute configuration of AAs among peptide drugs and detect trace levels of-AAs in complex biological samples. These results indicated that [d0]/[d5]-17β-EBC may contribute to entail a valuable step forward in peptide drug quality control and discovering chiral disease biomarkers.
- Li, Yuling,Zhou, Bowen,Wang, Keke,Zhang, Jing,Sun, Wenjian,Zhang, Li,Guo, Yinlong
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p. 13589 - 13596
(2021/10/21)
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- In Situ Electrochemical Monitoring of Caged Compound Photochemistry: An Internal Actinometer for Substrate Release
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Caged compounds are molecules that release a protective substrate to free a biologically active substrate upon treatment with light of sufficient energy and duration. A notable limitation of this approach is difficulty in determining the degree of photoactivation in tissues or opaque solutions because light reaching the desired location is obstructed. Here, we have addressed this issue by developing an in situ electrochemical method in which the amount of caged molecule photorelease is determined by fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes. Using p-hydroxyphenyl glutamate (pHP-Glu) as our model system, we generated a linear calibration curve for oxidation of 4-hydroxyphenylacetic acid (4HPAA), the group from which the glutamate molecule leaves, up to a concentration of 1000 μM. Moreover, we are able to correct for the presence of residual pHP-Glu in solution as well as the light artifact that is produced. A corrected calibration curve was constructed by photoactivation of pHP-Glu in a 3 μL photoreaction vessel and subsequent analysis by high-performance liquid chromatography. This approach has yielded a linear relationship between 4HPAA concentration and oxidation current, allowing the determination of released glutamate independent of the amount of light reaching the chromophore. Moreover, we have successfully validated the newly developed method by in situ measurement in a whole, intact zebrafish brain. This work demonstrates for the first time the in situ electrochemical monitoring of caged compound photochemistry in brain tissue with FSCV, thus facilitating analyses of neuronal function.
- Jarosova, Romana,Kaplan, Sam V.,Field, Thomas M.,Givens, Richard S.,Senadheera, Sanjeewa N.,Johnson, Michael A.
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p. 2776 - 2784
(2021/02/16)
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- Isolation, Structure Determination, and Total Synthesis of Hoshinoamide C, an Antiparasitic Lipopeptide from the Marine Cyanobacterium Caldora penicillata
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Hoshinoamide C (1), an antiparasitic lipopeptide, was isolated from the marine cyanobacterium Caldora penicillata. Its planar structure was elucidated by spectral analyses, mainly 2D NMR, and the absolute configurations of the α-amino acid moieties were determined by degradation reactions followed by chiral-phase HPLC analyses. To clarify the absolute configuration of an unusual amino acid moiety, we synthesized two possible diastereomers of hoshinoamide C and determined its absolute configuration based on a comparison of their spectroscopic data with those of the natural compound. Hoshinoamide C (1) did not exhibit any cytotoxicity against HeLa or HL60 cells at 10 μM, but inhibited the growth of the parasites responsible for malaria (IC50 0.96 μM) and African sleeping sickness (IC50 2.9 μM).
- Iwasaki, Arihiro,Ohtomo, Keisuke,Kurisawa, Naoaki,Shiota, Ikuma,Rahmawati, Yulia,Jeelani, Ghulam,Nozaki, Tomoyoshi,Suenaga, Kiyotake
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p. 126 - 135
(2021/01/13)
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- The visible-light-driven transfer hydrogenation of nicotinamide cofactors with a robust ruthenium complex photocatalyst
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The highly efficient regeneration of nicotinamide cofactors has been successfully achieved with a quantum yield (Φ) of 7.9 × 10-3via photocatalytic transfer hydrogenation in the presence of the ruthenium complex Ru(tpy)(biq)Cl2 (where tpy = 2,2′:6′,2′′-terpyridine and biq = 2,2′-bisquinoline). The photocatalytic system is not only highly efficient but also tolerant to amino acid residues. The combination of this photocatalyst with glutamate dehydrogenase enabled the controllable and efficient synthesis of l-glutamate to be realized. A mechanism involving light-induced ligand exchange, decarboxylation and hydride transfer has been proposed. Kinetic isotope experiments revealed that the decarboxylation of [Ru(tpy)(biq)HCOO]+ to [Ru(tpy)(biq)H]+ was the rate-determining step with a small apparent activation energy of 3.2 ± 0.4 kcal mol-1. The hydricity of [Ru(tpy)(biq)H]+ was estimated, via reaction equilibrium, to be 40 ± 3 kcal mol-1
- Chen, Fushan,Deng, Li,Dong, Wenjin,Tang, Jie,Xian, Mo,Zhao, Lijun
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p. 2279 - 2287
(2020/04/20)
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- Purification and characterization of L-glutaminase enzyme from camel liver: Enzymatic anticancer property
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L-Glutaminase has gained an important attention as glutamine-depleting enzyme in treatment of various cancers. Therefore, this study aimed to purify, characterize and investigate antitumor activity of L-glutaminase from camel liver mitochondria (CL-Glu), since no available information about CL-Glu from camel. CL-Glu was purified using cell fractionation, ultrafiltration, DEAE-and CM-cellulose chromatography columns. The purified CL-Glu was a monomer with a molecular weight of 70 ± 3 kDa, isoelectric point of 7.2, optimum temperature of 70 °C and it was active over a broad pH range with a pH optimum at pH 8.0. Its activity had a clear dependence on phosphate ions. The studied enzyme showed sigmoidal kinetics, indicated its allosteric behavior with Km of 36 ± 4 mM and Hill coefficient of 1.5 which suggested a positive cooperatively of active sites. The purified L-glutaminase exerted antitumor activity against different cell lines with the highest cytotoxic activity against Hepatocellular carcinoma cell line (HepG-2) with an IC50 value of 152 μg/ml. In conclusion, L-glutaminase was purified from camel liver using simple methods and its unique properties such as stability at both wide pH range and at high temperature along with its relatively low molecular weight, facilitated its usage in medical applications as antitumor drug.
- Maharem, Tahany M.,Emam, Manal A.,Said, Youssef A.
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p. 1213 - 1222
(2019/12/25)
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- Helices on Interdomain Interface Couple Catalysis in the ATPPase Domain with Allostery in Plasmodium falciparum GMP Synthetase
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GMP synthetase catalyses the conversion of XMP to GMP through a series of reactions that include hydrolysis of Gln to generate ammonia in the glutamine amidotransferase (GATase) domain, activation of XMP to adenyl-XMP intermediate in the ATP pyrophosphatase (ATPPase) domain and reaction of ammonia with the intermediate to generate GMP. The functioning of GMP synthetases entails bidirectional domain crosstalk, which leads to allosteric activation of the GATase domain, synchronization of catalytic events and tunnelling of ammonia. Herein, we have taken recourse to the analysis of structures of GMP synthetases, site-directed mutagenesis and steady-state and transient kinetics on the Plasmodium falciparum enzyme to decipher the molecular basis of catalysis in the ATPPase domain and domain crosstalk. Our results suggest an arrangement at the interdomain interface, of helices with residues that play roles in ATPPase catalysis as well as domain crosstalk enabling the coupling of ATPPase catalysis with GATase activation. Overall, the study enhances our understanding of GMP synthetases, which are drug targets in many infectious pathogens.
- Shivakumaraswamy, Santosh,Pandey, Nivedita,Ballut, Lionel,Violot, Sébastien,Aghajari, Nushin,Balaram, Hemalatha
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p. 2805 - 2817
(2020/06/25)
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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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- Fluorescence Detection of Prostate Cancer by an Activatable Fluorescence Probe for PSMA Carboxypeptidase Activity
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Prostate cancer (PCa) is a common malignant tumor among adult males, and convenient intraoperative detection of PCa would reduce the risk of leaving positive surgical margins, especially during nerve-sparing procedures. To achieve rapid, fluorescence-based visualization of PCa, we focused on the glutamate carboxypeptidase (CP) activity of prostate-specific membrane antigen (PSMA), a type II transmembrane glycoprotein that is attracting attention as a PCa biomarker. Based on our finding that aryl glutamate conjugates with an azoformyl linker are recognized by PSMA and have a sufficiently low LUMO (lowest unoccupied molecular orbital) energy level to quench the fluorophore through photoinduced electron transfer, we designed and synthesized a first-in-class activatable fluorescence probe for CP activity of PSMA. The developed probe allowed us to visualize the CP activity of PSMA in living cells and in clinical specimens from PCa patients and is expected to be useful for rapid intraoperative detection and diagnosis of PCa.
- Kawatani, Minoru,Yamamoto, Kyoko,Yamada, Daisuke,Kamiya, Mako,Miyakawa, Jimpei,Miyama, Yu,Kojima, Ryosuke,Morikawa, Teppei,Kume, Haruki,Urano, Yasuteru
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p. 10409 - 10416
(2019/07/04)
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- Easy-handling and low-leaching heterogeneous palladium and platinum catalysts via coating with a silicone elastomer
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We have developed a practical protocol for coating of commercial Pd/Al2O3 and Pt/Al2O3 catalysts in micro-powders with a silicone elastomer. Compared to original catalysts, the treated catalysts are easier to weight and transfer, and they are easier to recover by simple filtration. More importantly, the metal leaching of treated catalysts was significantly reduced. The treated catalysts worked very well in diverse hydrogenation reactions.
- Zhou, Mi,Li, Tingting,Xu, Bo
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supporting information
p. 948 - 952
(2019/03/08)
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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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- Comparative Study of Kinetic and Mechanistic Study of Oxidation of L-Alanine and L-Proline by Sodium Periodate Catalyzed by Osmium(VIII) in Micromolar Concentrations
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Abstract: The kinetics of oxidation of two aliphatic α-amino acids (AA), namely, alanine and proline by NaIO4 has been investigated in alkaline medium in the presence of osmium(VIII) catalyst at a constant ionic strength of 1.0 mol dm–3 and at 25°C. The reactions were very slow to be measured in the absence of the catalyst. The reactions have a first order with respect both to [Os(VIII)] and [NaIO4], and fractional order with respect to both [L-alanine] (Ala) and [L-proline](Pro). The reaction show negligible effect of dielectric constant and ionic strength of medium. Increasing [OH–] concentration was found to decrease the oxidation rates while mercuric acetate acts as scavenger for both the reactions. A plausible oxidation mechanism has been proposed and the rate law expression has been derived. Both spectral and kinetic evidences revealed formation of intermediate complexes between AA and Os(VIII) before the rate-controlling step. Kinetic investigations have revealed that the order of reactivity is Pro > Ala. The complex thus formed reacts with the oxidant [NaIO4] by an inner-sphere mechanism with formation of the oxidation products of the amino acids which were identified as the corresponding carboxylic compounds, ammonium ion and carbon dioxide. The activation parameters of the first order rate constants were evaluated and discussed.
- Madhu Gupta,Srivastava, Amrita,Srivastava, Sheila
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- Kyanamide, a new Ahp-containing depsipeptide from marine cyanobacterium Caldora penicillata
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Kyanamide (1), a new depsipeptide containing 3-amino-6-hydroxy-2-piperidone moiety, was isolated from the Caldora penicillata marine cyanobacterium collected in Okinawa. Its structure was determined by spectroscopic analysis and Marfey's analysis of acid hydrolysate. Kyanamide exhibited moderate cytotoxicity against HeLa S3 cells. 1 also exhibited potent protease inhibitory activity against elastase and chymotrypsin with IC50 values of 0.13 nM and 1.1 μM.
- Ozaki, Kaori,Iwasaki, Arihiro,Suenaga, Kiyotake,Teruya, Toshiaki
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p. 3382 - 3386
(2019/05/15)
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- Effect of the inserted active-site-covering lid loop on the catalytic activity of a mutant: B. subtilis γ-glutamyltransferase (GGT)
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Γ-Glutamylpeptides are compounds derived from the acylation of an amino acid or a short peptide by the γ-carboxyl carbon of the side chain of glutamic acid. Due to their altered chemico-physical and organoleptic properties, they may be interesting substitutes or precursors of parent compounds used in pharmaceutical, dietetic and cosmetic formulations. Some of them are naturally occurring flavor enhancers or are endowed with biological activities. Enzymatic approaches to the synthesis of γ-glutamyl derivatives based on the use of γ-glutamyltransferases (GGTs, EC 2.3.2.2) have been proposed, which should be able to alleviate the problems connected with the troublesome and low-yielding extraction from natural sources or the non-economical chemical synthesis, which requires protection/deprotection steps. With the aim of overcoming the current limitations in the use of GGTs as biocatalysts, a mutant GGT was investigated. The mutant GGT was obtained by inserting the active-site-covering lid loop of the E. coli GGT onto the structure of B. subtilis GGT. With respect to the wild-type enzyme, the mutant showed a more demanding substrate specificity and a low hydrolase activity. These results represent an attempt to correlate the structural features of a GGT to its different activities. However, the ability of the mutant enzyme to catalyze the subsequent addition of several γ-glutamyl units, inherited by the parent B. subtilis GGT, still represents a limitation to its full application as a biocatalyst for preparative purposes.
- Massone, Michela,Calvio, Cinzia,Rabuffetti, Marco,Speranza, Giovanna,Morelli, Carlo F.
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p. 34699 - 34709
(2019/11/14)
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- Chiral Metal–Organic Framework Hollow Nanospheres for High-Efficiency Enantiomer Separation
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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
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p. 1535 - 1538
(2018/06/26)
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- Identification of the new chymotrypsin inhibitor micropeptin 996 by metabolomics-guided analysis
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An untargeted metabolomics approach was used to investigate a cultured strain of Microcystis aeruginosa (UTEX LB2386) known to be a prolific producer of a diverse class of cyanopeptides. Identification of a putative new compound with a molecular weight of 996 led to the purification and structure elucidation of this new member of the micropeptin class of cyanopeptides. Micropeptin 996 displayed potent inhibition of the serine protease enzyme chymotrypisin relative to structurally related members of this class.
- Strangman, Wendy K.,Stewart, Allison K.,Herring, Megan C.,Wright, Jeffrey L.C.
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supporting information
p. 934 - 937
(2018/02/14)
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- Structural Diversity and Anticancer Activity of Marine-Derived Elastase Inhibitors: Key Features and Mechanisms Mediating the Antimetastatic Effects in Invasive Breast Cancer
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Three new 3-amino-6-hydroxy-2-piperidone (Ahp)-containing cyclic depsipeptides, named loggerpeptins A–C (1–3), along with molassamide (4), were discovered from a marine cyanobacterium, extending the structural diversity of this prevalent scaffold of cyanobacterial serine protease inhibitors. Molassamide, which contains a 2-amino-butenoic (Abu) unit in the cyclic core, was the most potent and selective analogue against human neutrophil elastase (HNE). Given the growing evidence supporting the role of HNE in breast cancer progression and metastasis, we assessed the cellular effects of compounds 3 and 4 in the context of targeting invasive breast cancer. Both compounds inhibited cleavage of the elastase substrate CD40 in biochemical assays; however, only 4 exhibited significant cellular activity. As CD40 and other receptor proteolytic processing culminates in NFκB activation, we assessed the effects of 4 on the expression of target genes, including ICAM-1. ICAM-1 is also a direct target of elastase and, in our studies, compound 4 attenuated both elastase-induced ICAM-1 gene expression and ICAM-1 proteolytic processing by elastase, revealing a potential dual effect on migration through modulation of gene expression and proteolytic processing. Molassamide also specifically inhibited the elastase-mediated migration of highly invasive triple-negative breast cancer cells.
- Al-Awadhi, Fatma H.,Paul, Valerie J.,Luesch, Hendrik
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p. 815 - 825
(2018/03/27)
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- CAGED COMPOUND, AND MANUFACTURING METHOD AND EXPRESSION METHOD OF CAGED COMPOUND
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PROBLEM TO BE SOLVED: To provide a caged compound excellent in light reactivity and dark place stability, and capable of deprotection by a visible light. SOLUTION: A caged compound is represented by the following general formula (1). In the general formula (1), R1 represents a hydrogen atom, a halogen atom, an alkyl group, an aryl group, a cyano group, an alkoxy group, a hydroxy group, or an alkylamino group, R2 represents an alkyl group or a hetero atom other than a nitrogen atom, R3 represents a hydrogen atom, a halogen atom or an alkyl group, X represents a monovalent anion, Y represents a monovalent organic group, Z represents a hydrogen atom or a monovalent organic group, and a represents 0 or 1, however a represents 0 when R2 represents the hetero atom other than the nitrogen atom. SELECTED DRAWING: None COPYRIGHT: (C)2019,JPOandINPIT
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Paragraph 0166; 0167
(2019/03/01)
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- Moderate UV Exposure Enhances Learning and Memory by Promoting a Novel Glutamate Biosynthetic Pathway in the Brain
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Sunlight exposure is known to affect mood, learning, and cognition. However, the molecular and cellular mechanisms remain elusive. Here, we show that moderate UV exposure elevated blood urocanic acid (UCA), which then crossed the blood-brain barrier. Single-cell mass spectrometry and isotopic labeling revealed a novel intra-neuronal metabolic pathway converting UCA to glutamate (GLU) after UV exposure. This UV-triggered GLU synthesis promoted its packaging into synaptic vesicles and its release at glutamatergic terminals in the motor cortex and hippocampus. Related behaviors, like rotarod learning and object recognition memory, were enhanced after UV exposure. All UV-induced metabolic, electrophysiological, and behavioral effects could be reproduced by the intravenous injection of UCA and diminished by the application of inhibitor or short hairpin RNA (shRNA) against urocanase, an enzyme critical for the conversion of UCA to GLU. These findings reveal a new GLU biosynthetic pathway, which could contribute to some of the sunlight-induced neurobehavioral changes. UV-induced upregulation of a small molecule feeds into an intraneuronal metabolic pathway for glutamate biosynthesis that can enhance learning and memory.
- Zhu, Hongying,Wang, Ning,Yao, Lei,Chen, Qi,Zhang, Ran,Qian, Junchao,Hou, Yiwen,Guo, Weiwei,Fan, Sijia,Liu, Siling,Zhao, Qiaoyun,Du, Feng,Zuo, Xin,Guo, Yujun,Xu, Yan,Li, Jiali,Xue, Tian,Zhong, Kai,Song, Xiaoyuan,Huang, Guangming,Xiong, Wei
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p. 1716 - 17,1727
(2018/05/16)
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- Natalenamides A–C, cyclic tripeptides from the termite-associated Actinomadura sp. RB99
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In recent years, investigations into the biochemistry of insect-associated bacteria have increased. When combined with analytical dereplication processes, these studies provide a powerful strategy to identify structurally and/or biologically novel compounds. Non-ribosomally synthesized cyclic peptides have a broad bioactivity spectrum with high medicinal potential. Here, we report the discovery of three new cyclic tripeptides: natalenamides A–C (compounds 1–3). These compounds were identified from the culture broth of the fungus-growing termite-associated Actinomadura sp. RB99 using a liquid chromatography (LC)/ultraviolet (UV)/mass spectrometry (MS)-based dereplication method. Chemical structures of the new compounds (1–3) were established by analysis of comprehensive spectroscopic methods, including one-dimensional (1H and13C) and two-dimensional (1H-1H-COSY, HSQC, HMBC) nuclear magnetic resonance spectroscopy (NMR), together with high-resolution electrospray ionization mass spectrometry (HR-ESIMS) data. The absolute configurations of the new compounds were elucidated using Marfey’s analysis. Through several bioactivity tests for the tripeptides, we found that compound 3 exhibited significant inhibitory effects on 3-isobutyl-1-methylxanthine (IBMX)-induced melanin production. The effect of compound 3 was similar to that of kojic acid, a compound extensively used as a cosmetic material with a skin-whitening effect.
- Lee, Seoung Rak,Lee, Dahae,Yu, Jae Sik,Benndorf, René,Lee, Sullim,Lee, Dong-Soo,Huh, Jungmoo,Wilhelm de Beer,Kim, Yong Ho,Beemelmanns, Christine,Kang, Ki Sung,Kim, Ki Hyun
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- Mild alkaline hydrolysis of hindered esters in non-aqueous solution
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Sterically hindered esters of carboxylic acids, which are considered very resistant to saponification, were rapidly and efficiently saponified in a non-aqueous medium using NaOH in MeOH/CH2Cl2 (1:9) at room temperature. Furthermore, this reaction protocol was extended and successfully applied to the hydrolysis of tosylates and N-tosyl indoles.
- Theodorou, Vassiliki,Alagiannis, Michalis,Ntemou, Nikoleta,Brentas, Alexios,Voulgari, Pinelopi,Polychronidou, Vasiliki,Gogou, Marina,Giannelos, Marios,Skobridis, Konstantinos
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p. 308 - 319
(2018/11/26)
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- Improved Synthesis of Caged Glutamate and Caging Each Functional Group
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Glutamate is an excitatory neurotransmitter that controls numerous pathways in the brain. Neuroscientists make use of photoremovable protecting groups, also known as cages, to release glutamate with precise spatial and temporal control. Various cage designs have been developed and amongst the most effective has been the nitroindolinyl caging of glutamate. We, hereby, report an improved synthesis of one of the current leading molecules of caged glutamate, 4-carboxymethoxy-5,7-dinitroindolinyl glutamate (CDNI-Glu), which possesses efficiencies with the highest reported quantum yield of at least 0.5. We present the shortest route, to date, for the synthesis of CDNI-Glu in 4 steps, with a total reaction time of 40 h and an overall yield of 20%. We also caged glutamate at the other two functional groups, thereby, introducing two new cage designs: α-CDNI-Glu and N-CDNI-Glu. We included a study of their photocleavage properties using UV-vis, NMR, as well as a physiology experiment of a two-photon uncaging of CDNI-Glu in acute hippocampal brain slices. The newly introduced cage designs may have the potential to minimize the interference that CDNI-Glu has with the GABAA receptor. We are broadly disseminating this to enable neuroscientists to use these photoactivatable tools.
- Guruge, Charitha,Ouedraogo, Yannick P.,Comitz, Richard Louis,Ma, Jingxuan,Losonczy, Attila,Nesnas, Nasri
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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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p. 1037 - 1042
(2017/07/25)
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- Tetrabutylammonium Fluoride as a Mild and Versatile Reagent for Cleaving Boroxazolidones to Their Corresponding Free α-Amino Acids
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Protection of α-amino acids with 9-borabicyclo[3.3.1]nonane (9-BBN) to give their corresponding boroxazolidones is highly attractive, as it concurrently masks both the amino and the carboxylic acid functionalities. However, the harsh methods required for deprotection of these boroxazolidones have limited their use. Herein, we report that tetrabutylammonium fluoride serves as a mild and versatile reagent that can be used to cleave boroxazolidones to their corresponding free α-amino acids. The reaction conditions were explored, including the use of various nucleophilic fluoride sources, solvents, and reaction temperatures. Nucleophilic fluoride sources comprising an ammonium cation proved superior to other countercations. The scope of the reaction was extended to the cleavage of B,B-diphenyl- and B,B-diethyl boroxazolidone complexes. Furthermore, a wide range of α-amino acid side-chain functionalities were shown to be compatible, including acids, esters, amides, thiols, thioethers, alkynes, phenols, basic heterocycles, and important biorelevant molecules such as glutathione, (S)-adenosyl-l-homocysteine, and l-biocytin.
- Poulie, Christian B. M.,Bunch, Lennart
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supporting information
p. 1475 - 1478
(2017/04/01)
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- Processing 2-Methyl- l -Tryptophan through Tandem Transamination and Selective Oxygenation Initiates Indole Ring Expansion in the Biosynthesis of Thiostrepton
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Thiostrepton (TSR), an archetypal member of the family of ribosomally synthesized and post-translationally modified thiopeptide antibiotics, possesses a biologically important quinaldic acid (QA) moiety within the side-ring system of its characteristic thiopeptide framework. QA is derived from an independent l-Trp residue; however, its associated transformation process remains poorly understood. We here report that during the formation of QA, the key expansion of an indole to a quinoline relies on the activities of the pyridoxal-5′-phosphate-dependent protein TsrA and the flavoprotein TsrE. These proteins act in tandem to process the precursor 2-methyl- l-Trp through reversible transamination and selective oxygenation, thereby initiating a highly reactive rearrangement in which selective C2-N1 bond cleavage via hydrolysis for indole ring-opening is closely coupled with C2′-N1 bond formation via condensation for recyclization and ring expansion in the production of a quinoline ketone intermediate. This indole ring-expansion mechanism is unusual, and represents a new strategy found in nature for l-Trp-based functionalization.
- Lin, Zhi,Ji, Jia,Zhou, Shuaixiang,Zhang, Fang,Wu, Jiequn,Guo, Yinlong,Liu, Wen
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supporting information
p. 12105 - 12108
(2017/09/12)
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- Bacilotetrins A and B, Anti-Staphylococcal Cyclic-Lipotetrapeptides from a Marine-Derived Bacillus subtilis
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LC-MS and NMR spectroscopy guided metabolic profiling and dereplication of a crude extract obtained from the fermentation of a marine-derived bacterium, Bacillus subtilis, followed by chromatographic isolation yielded two new cyclic-lipotetrapeptides, bacilotetrins A (1) and B (2). Based on extensive 1D and 2D NMR and high-resolution ESIMS data analysis, the structures of 1 and 2 were elucidated, revealing the unique structures of these lipopeptides consisting of three leucines and a glutamic acid residue cyclized with a lipophilic 3-hydroxy fatty acid. The absolute stereochemistries at selected stereocenters in 1 and 2 were assigned by chemical derivatization and comparison to literature data. Compounds 1 and 2 exhibited anti-MRSA activity with MIC values of 8 to 32 μg/mL. However, these compounds showed no cytotoxicity when tested against prostate and liver cancer cell lines using the standard SRB assay.
- Tareq, Fakir Shahidullah,Shin, Hee Jae
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p. 2889 - 2892
(2017/12/01)
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- Synthesis of ortho-carboranyl derivatives of (S)-asparagine and (S)-glutamine
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(S)-Asparagine and (S)-glutamine ortho-carboranyl derivatives with free amino and carboxy groups in the α-position were synthesized. By an example of Nγ-(1,2-dicarba-closo-dodecarboran-3-yl)-(S)-glutamine it was demonstrated that the developed synthetic approach carboranyl derivatives of amino acids allowed the preparation of optically pure isomers.
- Gruzdev,Levit,Olshevskaya,Krasnov
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p. 769 - 776
(2017/07/07)
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- Purification, structural characterization and bioactivity evaluation of a novel proteoglycan produced by Corbicula fluminea
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A novel proteoglycan, named CFPS-11, was isolated from Corbicula fluminea, which is a food source of freshwater bivalve mollusk. CFPS-11 had an average molecular weight of 807.7 kDa and consisted of D-glucose and D-glucosamine in a molar ratio of 12.2:1.0. The protein moiety (~5%) of CFPS-11 was covalently bonded to the polysaccharide chain in O-linkage type through both serine and thereonine residues. The polysaccharide chain of CFPS-11 was composed of (1 → 4)-α-D-glucopyranosyl and (1 → 3,6)-α-D-glucopyranosyl residues, which branched at O-6. The branch chain consisted of (1 →)-α-D-glucopyranosyl and (1 →)-α-D-N-acetylglucosamine residues. CFPS-11 exhibited significant antioxidant activity in a dose-dependent manner and remarkable inhibition activities against α-amylase and α-glucosidase by in vitro assays. These findings indicated that the CFPS-11 from C. fluminea has the potential for development as a health food ingredient.
- Yan, Jing-Kun,Wang, Yao-Yao,Qiu, Wen-Yi,Wu, Li-Xia,Ding, Zhi-Chao,Cai, Wu-Dan
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- Inhibitors of serine proteases from a Microcystis sp. Bloom material collected from timurim reservoir, Israel
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Two new natural products, micropeptin TR1058 (1) and aeruginosin TR642 (2), were isolated from the hydrophilic extract of bloom material of Microcystis sp. collected from the Timurim water reservoir in Israel. The structures of compounds 1 and 2 were determined using 1D and 2D NMR spectroscopy and HR ESI MS and MS/MS techniques. Micropeptin TR1058 (1) was extremely unstable under the isolation conditions, and several degradation products were identified. NMR analysis of aeruginosin TR642 (2) revealed a mixture of eight isomers, and elucidation of its structure was challenging. Aeruginosin TR642 contains a 4,5-didehydroaraginal subunit that has not been described before. Micropeptin TR1058 (1) inhibited chymotrypsin with an IC50 of 6.78 μM, and aeruginosin TR642 (2) inhibited trypsin and thrombin with inhibition concentration (IC50) values of 3.80 and 0.85 μM, respectively. The structures and biological activities of the new compounds are discussed.
- Hasan-Amer, Rawan,Carmeli, Shmuel
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- Characterization of aromatic aminotransferases from Ephedra sinica Stapf
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Ephedra sinica Stapf (Ephedraceae) is a broom-like shrub cultivated in arid regions of China, Korea and Japan. This plant accumulates large amounts of the ephedrine alkaloids in its aerial tissues. These analogs of amphetamine mimic the actions of adrenaline and stimulate the sympathetic nervous system. While much is known about their pharmacological properties, the mechanisms by which they are synthesized remain largely unknown. A functional genomics platform was established to investigate their biosynthesis. Candidate enzymes were obtained from an expressed sequence tag collection based on similarity to characterized enzymes with similar functions. Two aromatic aminotransferases, EsAroAT1 and EsAroAT2, were characterized. The results of quantitative reverse transcription-polymerase chain reaction indicated that both genes are expressed in young stem tissue, where ephedrine alkaloids are synthesized, and in mature stem tissue. Nickel affinity-purified recombinant EsAroAT1 exhibited higher catalytic activity and was more homogeneous than EsAroAT2 as determined by size-exclusion chromatography. EsAroAT1 was highly active as a tyrosine aminotransferase with α-ketoglutarate followed by α-ketomethylthiobutyrate and very low activity with phenylpyruvate. In the reverse direction, catalytic efficiency was similar for the formation of all three aromatic amino acids using l-glutamate. Neither enzyme accepted putative intermediates in the ephedrine alkaloid biosynthetic pathway, S-phenylacetylcarbinol or 1-phenylpropane-1,2-dione, as substrates.
- Kilpatrick, Korey,Pajak, Agnieszka,Hagel, Jillian M.,Sumarah, Mark W.,Lewinsohn, Efraim,Facchini, Peter J.,Marsolais, Frédéric
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p. 1209 - 1220
(2016/04/26)
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- Asymmetric Transamination of α-Keto Acids Catalyzed by Chiral Pyridoxamines
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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
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supporting information
p. 3658 - 3661
(2016/08/16)
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- A novel thyroglobulin-binding lectin from the brown alga Hizikia fusiformis and its antioxidant activities
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A lectin (HFL) was isolated from the brown alga, Hizikia fusiformis, through ion exchange on cellulose DE52 and HPLC with a TSK-gel G4000PWXL column. SDS-PAGE showed that HFL had a molecular mass of 16.1 kDa. The HPLC (with a TSK-gel G4000PWXL column) indicated that HFL is a tetramer in its native state. The total carbohydrate content was 41%. Glucose, galactose and fucose were the monosaccharide units of HFL, and the normalized mol% values were 6, 14 and 80, respectively. HFL contains a large amount of the acidic amino acid, Asx. The β-elimination reaction suggested that the oligosaccharide and peptide moieties of HFL may belong to the N-glucosidic linkage. The amino acid sequences, of about five segments of HFL, were acquired by MALDI-TOF/TOF, and the sequences have no homology with other lectins. HFL was found to agglutinate sheep erythrocytes. The hemagglutination activity was inhibited by thyroglobulin, from bovine thyroid, but not by any of the monosaccharides tested. The lectin reaction was independent of the presence of the divalent cation Ca2+. HFL showed free radical scavenging activity against hydroxyl, DPPH and ABTS+ radicals.
- Wu, Mingjiang,Tong, Changqing,Wu, Yue,Liu, Shuai,Li, Wei
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- NATURAL FLAVOUR ENHANCERS AND THE METHOD FOR MAKING SAME
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The present invention pertains to the use of certain flavor enhancing compounds obtainable from an Allium species. In one embodiment, seeds from chives, leeks, ramson and other onions are used for conveying strong kokumi flavor enhancing effects on food products without imparting an onion or garlic-like off taste. These flavor enhancing compounds are also useful for the preparation of Amadori products, which are also used as kokumi flavor enhancing compounds.
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Paragraph 0029
(2016/07/27)
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- A simple and sensitive detection of glutamic-pyruvic transaminase activity based on fluorescence quenching of bovine serum albumin
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It is well known that Cu(ii) can coordinate with l-alanine (Cu-Ala), which can be destroyed through the addition of glutamic-pyruvic transaminase (GPT) since GPT can effectively catalyze the conversion of l-alanine into keto-acetic acid. As a result, the free Cu(ii) ion can combine with bovine serum albumin (BSA) and in turn quench the fluorescence of BSA. In this context, a simple and sensitive GPT activity detection via fluorescence quenching method has been developed. The fluorescence intensity of the system shows a linear relationship with the GPT concentration in the range of 5 and 400 U L-1 with a detection limit down to 3 U L-1 (S/N = 3). Avoiding any labels or complicated operations, this cost-effective and convenient method holds the potential for the rapid diagnosis of GPT-related diseases.
- Chen, Miao,Rong, Liya,Chen, Xiaoqing
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p. 103557 - 103562
(2015/12/23)
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- An easy 'Filter-and-Separate' method for enantioselective separation and chiral sensing of substrates using a biomimetic homochiral polymer
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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
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supporting information
p. 8931 - 8934
(2015/05/27)
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- Characterization of two putative prolinases (PepR1 and PepR2) from Lactobacillus plantarum WCFS1: Occurrence of two isozymes with structural similarity and different catalytic properties
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Two putative prolinases (PepR1 and PepR2) of Lactobacillus plantarum WCSF1 share 48.5% amino acid sequence identity (55.5% at the DNA level); however, PepR1 exhibits over 80% identity at the protein level with other lactobacilli prolinases while PepR2 exhibits only 51% or less identity. In this study, the putative genes were overexpressed in Escherichia coli, purified to gel electrophoretic homogeneity, and then characterized. Purified PepR1 and PepR2 hydrolysed Pro-Xaa dipeptide substrates at similar rates, proving their nature as prolinases. Structural analyses using circular dichroism, dynamic light scattering, gel filtration, and molecular modelling revealed that the two prolinases have similar structural characteristics: high β-sheet content, homotetrameric structure, and similar folding to the PepI/PepL/PepR peptidase family. However, kinetic and thermodynamic analyses of PepR1 and PepR2 indicated differences in many aspects: optimum temperatures (25 and 30 °C, respectively), optimum pH (pH 7.5 and 8.0, respectively), substrate specificities (high stringency of PepR2), kinetic parameters, and thermal stability (29 and 48 °C, respectively). Also, these prolinases behaved differently towards inhibitor treatments, suggesting structural and/or functional differences in their active sites. Differences in the two prolinases would contribute to a diversity of catalytic activities, so that they work together cooperatively and complementarily to hydrolyse proline-containing peptides with broader specificity, working pH, working temperature, and higher efficiency, thus allowing adaptation to a wider range of environments.
- Huang, Yanyu,Tanaka, Takuji
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- Site-specific labeling of synthetic peptide using the chemoselective reaction between N-methoxyamino acid and isothiocyanate
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Site-specific labeling of synthetic peptides carrying N-methoxyglycine (MeOGly) by isothiocyanate is demonstrated. A nonapeptide having MeOGly at its N-terminus was synthesized by the solid-phase method and reacted with phenylisothiocyanate under various conditions. In acidic solution, the reaction specifically gave a peptide having phenylthiourea structure at its N-terminus, leaving side chain amino group intact. The synthetic human β-defensin-2 carrying MeOGly at its N-terminus or the side chain amino group of Lys10 reacted with phenylisothiocyanate or fluorescein isothiocyanate also at the N-methoxyamino group under the same conditions, demonstrating that this method is generally useful for the site-specific labeling of linear synthetic peptides as well as disulfide-containing peptides.
- Hara, Toshiaki,Purwati, Euis Maras,Tainosyo, Akira,Kawakami, Toru,Hojo, Hironobu,Aimoto, Saburo
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p. 765 - 769
(2015/09/21)
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- A thermodynamic insight into the recognition of hydrophilic and hydrophobic amino acids in pure water by aza-scorpiand type receptors
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Interactions of different hydrophilic (His, Asp, Glu,) and hydrophobic (Ala, Phe, Tyr, Trp) amino acids in water with a scorpiand aza-macrocycle (L1) containing a pyridine group in the ring and its derivative (L2) bearing a naphthalene group in the tail have been analysed by potentiometric and calorimetric measurements. Theoretical calculations corroborate that major attractive forces that hold the adduct together are hydrogen bonds and salt-bridges, even though other interactions such as π-stacking or NH+...π may contribute in the case of hydrophobic amino acids and L2. Calorimetric measurements indicate that the interactions between L1 and the different amino acids are principally driven by entropy, often associated with solvation/desolvation processes.
- Blasco, Salvador,Verdejo, Begoa,Bazzicalupi, Carla,Bianchi, Antonio,Giorgi, Claudia,Soriano, Concepcin,Garca-Espaa, Enrique
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p. 843 - 850
(2015/02/19)
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- Gageopeptins A and B, new inhibitors of zoospore motility of the phytopathogen Phytophthora capsici from a marine-derived bacterium Bacillus sp. 109GGC020
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Abstract The motility of zoospores is critical in the disease cycles of the peronosporomycetes that cause devastating diseases in plants, fishes, vertebrates, and microbes. In the course of screening for secondary metabolites regulating the motility of zoospores of Phytophthora capsici, we discovered two new inhibitors from the ethyl acetate extract of the fermentation broth of a marine-derived strain Bacillus sp. 109GGC020. The structures of these novel metabolites were elucidated as new cyclic lipopeptides and named gageopeptins A (1) and B (2) by spectroscopic analyses including high resolution MS and extensive 1D and 2D NMR. The stereoconfigurations of 1 and 2 were assigned based on the chemical derivatization studies and reviews of the literature data. Although compounds 1 and 2 impaired the motility of zoospores of P. capsici in dose- and time-dependent manners, compound 1 (IC50 = 1 μg/ml) was an approximately 400-fold stronger motility inhibitor than 2 (IC50 = 400 μg/ml). Interestingly, the zoospores halted by compound 1 were subsequently lysed at higher concentrations (IC50 = 50 μg/ml). Compounds 1 and 2 were also tested against some bacteria and fungi by broth dilution assay, and exhibited moderate antibacterial and good antifungal activities.
- Tareq, Fakir Shahidullah,Hasan, Choudhury M.,Lee, Hyi-Seung,Lee, Yeon-Ju,Lee, Jong Seok,Surovy, Musrat Zahan,Islam, Md. Tofazzal,Shin, Hee Jae
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p. 3325 - 3329
(2015/07/08)
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- Isolation, Characterization, and Synthesis of the Barrettides: Disulfide-Containing Peptides from the Marine Sponge Geodia barretti
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Two disulfide-containing peptides, barrettides A (1) and B (2), from the cold-water marine sponge Geodia barretti are described. Those 31 amino acid residue long peptides were sequenced using mass spectrometry methods and structurally characterized using NMR spectroscopy. The structure of 1 was confirmed by total synthesis using the solid-phase peptide synthesis approach that was developed. The two peptides were found to differ only at a single position in their sequence. The three-dimensional structure of 1 revealed that these peptides possess a unique fold consisting of a long β-hairpin structure that is cross-braced by two disulfide bonds in a ladder-like arrangement. The peptides are amphipathic in nature with the hydrophobic and charged residues clustered on separate faces of the molecule. The barrettides were found not to inhibit the growth of either Escherichia coli or Staphylococcus aureus but displayed antifouling activity against barnacle larvae (Balanus improvisus) without lethal effects in the concentrations tested. (Figure Presented).
- Carstens, Bodil B.,Rosengren, K. Johan,Gunasekera, Sunithi,Schempp, Stefanie,Bohlin, Lars,Dahlstr?m, Mia,Clark, Richard J.,G?ransson, Ulf
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p. 1886 - 1893
(2015/09/08)
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- Enantiospecific C-H Activation Using Ruthenium Nanocatalysts
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The activation of C-H bonds has revolutionized modern synthetic chemistry. However, no general strategy for enantiospecific C-H activation has been developed to date. We herein report an enantiospecific C-H activation reaction followed by deuterium incorporation at stereogenic centers. Mechanistic studies suggest that the selectivity for the α-position of the directing heteroatom results from a four-membered dimetallacycle as the key intermediate. This work paves the way to novel molecular chemistry on nanoparticles.
- Taglang, Céline,Martínez-Prieto, Luis Miguel,Del Rosal, Iker,Maron, Laurent,Poteau, Romuald,Philippot, Karine,Chaudret, Bruno,Perato, Serge,Sam Lone, Ana?s,Puente, Céline,Dugave, Christophe,Rousseau, Bernard,Pieters, Grégory
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supporting information
p. 10474 - 10477
(2015/09/02)
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- Rapid, effective deprotection of tert-butoxycarbonyl (Boc) amino acids and peptides at high temperatures using a thermally stable ionic liquid
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A method for high temperature Boc deprotection of amino acids and peptides in a phosphonium ionic liquid is described. The ionic liquid had low viscosity, high thermal stability and demonstrated a beneficial effect. The study extended the possibility for extraction of water soluble polar organic molecules using ionic liquids. Trace water significantly improved product purity and yield, while only 2 equiv. TFA led to deprotection within 10 min. The trityl group was also deprotected.
- Bhawal, Sumit S.,Patil, Rahul A.,Armstrong, Daniel W.
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p. 95854 - 95856
(2015/11/24)
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- Biocatalytic photosynthesis with water as an electron donor
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Efficient harvesting of unlimited solar energy and its conversion into valuable chemicals is one of the ultimate goals of scientists. With the ever-increasing concerns about sustainable growth and environmental issues, numerous efforts have been made to develop artificial photosynthetic process for the production of fuels and fine chemicals, thus mimicking natural photosynthesis. Despite the research progress made over the decades, the technology is still in its infancy because of the difficulties in kinetic coupling of whole photocatalytic cycles. Herein, we report a new type of artificial photosynthesis system that can avoid such problems by integrally coupling biocatalytic redox reactions with photocatalytic water splitting. We found that photocatalytic water splitting can be efficiently coupled with biocatalytic redox reactions by using tetracobalt polyoxometalate and Rh-based organometallic compound as hole and electron scavengers, respectively, for photoexcited [Ru(bpy)3]2+. Based on these results, we could successfully photosynthesize a model chiral compound (L-glutamate) using a model redox enzyme (glutamate dehydrogenase) upon in situ photoregeneration of cofactors.
- Ryu, Jungki,Nam, Dong Heon,Lee, Sahng Ha,Park, Chan Beum
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p. 12020 - 12025
(2015/03/31)
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- β-hairpin peptidomimetics
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β-Hairpin peptidomimetics of the general formula Cyclo(-Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-Xaa10-Xaa11-Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-), and pharmaceutically acceptable salts thereof, with Xaa 1-Xaa 16 being amino acid residues of certain types which are defined in the description and the claims, have CXCR4 antagonizing properties and prolonged half-lives in vivo and can be used for preventing HIV infections in healthy individuals or for slowing and halting viral progression in infected patients; or where cancer is mediated or resulting from CXCR4 receptor activity; or where immunological diseases are mediated or resulting from CXCR4 receptor activity; or for treating immunosuppression; or during apheresis collections of peripheral blood stem cells and/or as agents to induce mobilization of stem cells to regulate tissue repair. These peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.
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- β-hairpin peptidomimetics
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β-Hairpin peptidomimetics of the general formula Cyclo(-Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-Xaa10-Xaa11-Xaa12-Xaa13-Xaa14-), enantiomers and pharmaceutically acceptable salts thereof, with Xaa1-Xaa14 being amino acid residues of certain types which are defined in the description and the claims, have anti-infective activity, e.g. to selectively inhibit the growth of or to kill microorganisms such as Bacillus subtilis and/or Shigella boydii. They can be used as medicaments to treat or prevent infections or as disinfectants for foodstuffs, cosmetics, medicaments or other nutrient-containing materials. These peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.
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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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