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Strain KMM 9513T was isolated from a sediment sample collected from the Sea of Japan seashore and selected due to its ability to inhibit indicator bacterial growth. The strain KMM 9513T has been recently described as a novel species Rheinheimera japonica. This study was undertaken to determine which substances produced by strain KMM 9513T could be responsible for its antimicrobial activity. Eight compounds were obtained from an ethyl acetate extract of R. japonica KMM 9513T. The structures of five diketopiperazines (4?8) and diisobutyl-, dibutyl- and bis(2-ethylhexyl) phthalates (1?3) were established on the basis of detailed interpretation of NMR data, by Marfey method and optical rotation data. The structures of diketopiperazines were determined as cyclo-(l-valyl-l-proline), cyclo-(l-valyl-d-proline), cyclo-(l-phenylalanyl-l-proline), cyclo-(l-leucyl-l-proline), and cyclo-(l-phenylalanyl-d-proline). Compounds 1?3, 5 and 8 revealed antimicrobial activities against Bacillus subtilis and/or Enterococcus faecium and Staphylococcus aureus. In this paper, we describe the isolation and structural elucidation of the isolated compounds 1?8. This is the first report of the characterisation of low molecular weight antibacterial metabolites produced by a member of the genus Rheinheimera.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Sphingosine 1-phosphate (S1P) is a bioactive lipid that has been identified as an accelerant of cancer progression. The sphingosine kinases (SphKs) are the sole producers of S1P, and thus, SphK inhibitors may prove effective in cancer mitigation and chemosensitization. Of the two SphKs, SphK1 overexpression has been observed in a myriad of cancer cell lines and tissues and has been recognized as the presumptive target over that of the poorly characterized SphK2. Herein, we present the design and synthesis of amidine-based nanomolar SphK1 subtype-selective inhibitors. A homology model of SphK1, trained with this library of amidine inhibitors, was then used to predict the activity of additional, more potent, inhibitors. Lastly, select amidine inhibitors were validated in human leukemia U937 cells, where they significantly reduced endogenous S1P levels at nanomolar concentrations.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Background: The sigma54 factor controls unique promoters and interacts with a specialized activator (enhancer binding proteins [EBP]) for transcription initiation. Although sigma54 is present in many Clostridiales species that have great importance in human health and biotechnological applications, the cellular processes controlled by sigma54 remain unknown. Results: For systematic analysis of the regulatory functions of sigma54, we performed comparative genomic reconstruction of transcriptional regulons of sigma54 in 57 species from the Clostridiales order. The EBP-binding DNA motifs and regulated genes were identified for 263 EBPs that constitute 39 distinct groups. The reconstructed sigma54 regulons contain the genes involved in fermentation and amino acid catabolism. The predicted sigma54 binding sites in the genomes of Clostridiales spp. were verified by in vitro binding assays. To our knowledge, this is the first report about direct regulation of the Stickland reactions and butyrate and alcohols synthesis by sigma54 and the respective EBPs. Considerable variations were demonstrated in the sizes and gene contents of reconstructed sigma54 regulons between different Clostridiales species. It is proposed that sigma54 controls butyrate and alcohols synthesis in solvent-producing species, regulates autotrophic metabolism in acetogenic species, and affects the toxin production in pathogenic species. Conclusions: This study reveals previously unrecognized functions of sigma54 and provides novel insights into the regulation of fermentation and amino acid metabolism in Clostridiales species, which could have potential applications in guiding the treatment and efficient utilization of these species.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Recently, the demand for D-amino acid profiling has been drastically increasing because the significance of D-amino acid in various biological events is suggested. However, the present methodologies for D-amino acid profiling are still unsatisfactory. Therefore, a highly sensitive, robust, high-throughput, and user-friendly method for D-amino acid profiling must be developed. In this paper, we developed a novel method for D-amino acid profiling using a combination of a chiral column and time of flight mass spectrometry (TOFMS). To our knowledge, our approach has the best performance for D-amino acid analysis that includes the shortest analytical time (within 10 min), the highest enantioseparability without derivatization, and the largest coverage for analytical targets (more than one hundred targets including non-proteinogenic amino acids and amines). Thus, our novel profiling method will be instrumental in advancing the D-amino acid research in the future.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Liquid chromatography coupled with mass spectrometry (LC-MS) is one of the most prominent analytical techniques due to its inherent selectivity and sensitivity. LC-MS is currently the first choice for high-throughput bioanalysis due to the advancements in MS instruments and the analytical software. Based on this situation, we are developing various types of derivatization reagents, including chiral reagents for MS and/or MS/MS detection. These developed reagents are adopted for the detection of biomarker candidates related to diseases. The biomarker candidates include not only achiral molecules, but also chiral ones. Although determining the already-identified chiral molecules is relative easy, it is very difficult to identify and/or determine unknown enantiomer(s) in real samples. To solve this difficulty, we proposed a new strategy to identify unknown enantiomeric biomarkers related to diseases. This review paper deals with the development of derivatization reagents for amines and carboxylic acids in LC-MS analysis and their application to bioanalysis.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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The chiral discrimination ability of permethylated glucopyrano-oligosaccharides toward amino acid 2-propyl ester hydrochlorides was evaluated using FAB mass spectrometry. In the given permethylated homo-oligosaccharides, permethylated beta-cello-oligosaccharide series (II) showed remarkably higher S-selectivity toward tryptophan ester salts (Trp-O-iPr+) independent of the numbers (n) of the glucopyranose unit (n = 2-5). The hexamer and heptamer of the permethylated beta-malto-oligosaccharide series (I) showed the very similar enantioselectivity to permethylated alpha- and beta-cyclodextrin.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Verlamelin and its new derivative (verlamelin B) were isolated from fermentation broth of entomopathogenic fungus Lecanicillium sp. HF627. As the structural elucidation of verlamelin so far was only preliminary, we studied and determined the absolute structure of these two compounds to be cyclo(5S-hydroxytetradecanoic acid-D-alloThr/Ser-D-Ala-L-Pro-L-Gln-D-Tyr-L-Val). This is the first study that precisely analyzed the structure of verlamelin.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Compounds of formula (I) wherein R1 to R4, X and A are as defined in the claims and pharmaceutically acceptable salts and esters thereof, are disclosed. The compounds of formula (I) possess utility as tissue-selective androgen receptor modulators (SARM) and are useful in hormonal therapy, e.g. in the treatment or prevention of male hypogonadism and age-related conditions such as andropause.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Untargeted metabolomics aims to comprehensively profile metabolites as many as possible in biological samples. Recently, ion mobility-mass spectrometry (IM-MS) has emerged as a powerful technology for untargeted metabolomics. The emerging role of IM-MS in untargeted metabolomics enables the separation of metabolite isomers and generation of multidimension data to support the identification of metabolites. In this review, we first introduced the basic principles of IM-MS instruments commonly used for untargeted metabolomics. Then, we demonstrated the application of IM-MS for metabolite separation and identification of both known and unknown metabolites. Finally, we discussed the future developments of IM-MS technology to improve untargeted metabolomics.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Two-dimensional high-performance liquid chromatographic (2D-HPLC) and 2D-HPLC-mass spectrometric (2D-HPLC?MS) systems have been designed and developed for the determination of the citrulline (Cit) and ornithine (Orn) enantiomers. Several D-amino acids have already been identified as novel physiologically active molecules and biomarkers, and the enantioselective evaluation of the amounts, distributions and metabolisms of non-proteinogenic amino acids gain as well increasing interest. In the present study, highly selective analytical methods were developed using a capillary monolithic ODS column (0.53 mm i.d. x 1000 mm) for the reversed-phase separation of the target analytes from the matrix compounds in the first dimension, and a narrowbore-Pirkle type enantioselective column, KSAACSP?105 S (1.5 mm i.d. x 250 mm), was used for the enantiomer separation in the second dimension. The amino acids were analyzed after pre-column derivatization with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) and detected by the fluorescence detector and MS. The systems were applied to the urine of D-amino acid oxidase (DAO) deficient B6DAO? mice and control C57BL mice to evaluate the presence and metabolism of the Cit and Orn enantiomers in mammals. As a result, all of the 4 target enantiomers (D-Cit, L-Cit, D-Orn, L-Orn) were found in the urine of both strains. The %D value of Cit (D-Cit/Cit × 100) increased about 3-fold in the urine of the DAO deficient mice and that of Orn also tended to increase with the DAO deficiency. These results were definitely confirmed by a 2D-HPLC?MS detection system. Further investigations about the biological significance of these D-isomers are currently ongoing.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI