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https://www.readbyqxmd.com/read/29771530/evolution-of-biocatalytic-and-chemocatalytic-c-h-functionalization-strategy-in-the-synthesis-of-manzacidin-c
#1
Christian R Zwick, Hans Renata
Due to their unique molecular architecture, the manzacidins have been the subject of intense synthetic efforts in the past two decades. Here, we describe two synthetic approaches towards manzacidin C that center on the enzymatic hydroxylation of unprotected L-leucine. This study also resulted in the discovery of novel synthetic methodologies, including a photocatalytic C-H azidation of unprotected amino acids. Additionally, we describe the use of hydroxylated L-leucine in the preparation of various densely-substituted pyrrolidines...
May 17, 2018: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29765489/gallic-acid-l-leucine-conjugate-protects-mice-against-lps-induced-inflammation-and-sepsis-via-correcting-proinflammatory-lipid-mediator-profiles-and-oxidative-stress
#2
Yuanyuan Cheng, Xuechen Li, Hung-Fat Tse, Jianhui Rong
The pathology of endotoxin LPS-induced sepsis is hallmarked by aberrant production of proinflammatory lipid mediators and nitric oxide (NO). The aim of the present study was to determine whether the new product gallic acid-L-leucine (GAL) conjugate could ameliorate the LPS-induced dysregulation of arachidonic acid metabolism and NO production. We first investigated the effects of GAL conjugate on the expression of proinflammatory enzymes and the production of proinflammatory NO and lipid mediators in mouse macrophage cell line RAW264...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29702418/low-temperature-investigations-of-dynamic-properties-in-l-leucine-chloranilic-acid-complex
#3
J Hetmańczyk, J Nowicka-Scheibe, J K Maurin, A Pawlukojć
Inelastic neutron scattering (INS) and infra-red (IR) spectroscopy methods were used for determination of dynamic structure of l-leucine - chloranilic acid complex. A theoretical dynamic pattern calculated by the density functional theory (DFT) method for periodic boundary conditions accompanied the experimental ones. Normal modes in the vibrational spectra were defined and described. The characteristic presence of the Hadži's trio enriched by numerous submaxima is observed in the wavenumber range 3200-800 cm-1 ...
April 3, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/29687339/synthesis-and-characterization-of-a-hyperbranched-grafting-copolymer-pei-g-pleu-for-gene-and-drug-co-delivery
#4
Yanhui Li, Xue Zhang, Jingpeng Zhang, Xin Mu, Qian Duan, Tinghong Wang, Huayu Tian
L-Leucine (Leu) is a hydrophobic natural amino acid and can polymerize into poly-L-Leucine (PLeu) to be an excellent biocompatible material. In this paper, a hyperbranched copolymer polyethyleneimine-g-poly-L-leucine (PEI-g-PLeu) was synthesized by ring-opening polymerization with leucine NCA as monomer and PEI as initiator, which will be used as drug and gene co-delivery system for cancer therapy. To characterize the transfection efficiency in vitro, pGL3 as the reporter gene was loaded in PEI-g-PLeu to form complexes...
April 17, 2018: Journal of Materials Science. Materials in Medicine
https://www.readbyqxmd.com/read/29678544/influence-of-excipients-on-physical-and-aerosolization-stability-of-spray-dried-high-dose-powder-formulations-for-inhalation
#5
Nivedita Shetty, Heejun Park, Dmitry Zemlyanov, Sharad Mangal, Sonal Bhujbal, Qi Tony Zhou
The aim of this study is to investigate the influence of excipients on physical and aerosolization stability of spray dried Ciprofloxacin dry powder inhaler formulations. The model drug, Ciprofloxacin hydrochloride, was co-spray dried with excipients such as disaccharides (sucrose, lactose, trehalose), mannitol and L-leucine. The spray dried samples were stored at two different relative humidity (RH) conditions of: (1) 20% and (2) 55% RH at 20°C. Ciprofloxacin co-spray dried with disaccharides and L-leucine in the mass ratio of 1:1 demonstrated an increase in fine particle fraction (FPF) as compared with the spray dried Ciprofloxacin alone when stored at 20% RH...
April 17, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29674115/a-novel-l-leucine-5-hydroxylase-from-nostoc-piscinale-unravels-unexpected-sulfoxidation-activity-toward-l-methionine
#6
Dengyue Sun, Dengke Gao, Panpan Xu, Qianqian Guo, Zhangliang Zhu, Xiaotao Cheng, Song Bai, Hui-Min Qin, Fuping Lu
Hydroxy amino acids are produced by Fe(II)/αKG-dependent dioxygenases and used widely as medicinal intermediates for chemical synthesis. A novel l-leucine 5-hydroxylase gene from Nostoc piscinale (NpLDO) was cloned into pET28a (+), pColdI and pQE-80 L plasmids. Using a two-step purification process (Ni-affinity chromatography and gel filtration), highly purified recombinant NpLDO was obtained. Recombinant NpLDO displayed unexpectedly high sulfoxidation activity toward l-methionine. The reaction products were analyzed by high-performance liquid chromatography...
April 16, 2018: Protein Expression and Purification
https://www.readbyqxmd.com/read/29655797/pulmonary-administration-of-a-dry-powder-formulation-of-the-antifibrotic-drug-tilorone-reduces-silica-induced-lung-fibrosis-in-mice
#7
Ville Vartiainen, Janne Raula, Luis M Bimbo, Jenni Viinamäki, Janne T Backman, Nurcin Ugur, Esko Kauppinen, Eva Sutinen, Emmi Joensuu, Katri Koli, Marjukka Myllärniemi
The aim of this work was to study the antifibrotic effect of pulmonary administration of tilorone to lung fibrosis. L-leucine coated tilorone particles were prepared and their aerosolization properties were analyzed using two dry powder inhalers (Easyhaler and Twister). In addition, the biological activity and cell monolayer permeation was tested. The antifibrotic effect of tilorone delivered by oropharyngeal aspiration was studied in vivo using a silica-induced model of pulmonary fibrosis in mice in a preventive setting...
April 12, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29625212/development-and-characterization-of-high-payload-combination-dry-powders-of-anti-tubercular-drugs-for-treating-pulmonary-tuberculosis
#8
Basanth Babu Eedara, Bhamini Rangnekar, Shubhra Sinha, Colin Doyle, Alex Cavallaro, Shyamal C Das
This study aimed to develop a high payload dry powder inhalation formulation containing a combination of the first line anti-TB drug, pyrazinamide, and the second line drug, moxifloxacin HCl. Individual powders of pyrazinamide (PSD ) and moxifloxacin (MSD ) and combination powders of the two drugs without (PM) and with 10% L-leucine (PML) and 10% DPPC (PMLD) were produced by spray drying. PSD contained >10 μm crystalline particles and showed poor aerosolization behaviour with a fine particle fraction (FPF) of 18...
April 3, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29562689/gc-ms-based-endometabolome-analysis-differentiates-prostate-cancer-from-normal-prostate-cells
#9
Ana Rita Lima, Ana Margarida Araújo, Joana Pinto, Carmen Jerónimo, Rui Henrique, Maria de Lourdes Bastos, Márcia Carvalho, Paula Guedes de Pinho
Prostate cancer (PCa) is an important health problem worldwide. Diagnosis and management of PCa is very complex because the detection of serum prostate specific antigen (PSA) has several drawbacks. Metabolomics brings promise for cancer biomarker discovery and for better understanding PCa biochemistry. In this study, a gas chromatography-mass spectrometry (GC-MS) based metabolomic profiling of PCa cell lines was performed. The cell lines include 22RV1 and LNCaP from PCa with androgen receptor (AR) expression, DU145 and PC3 (which lack AR expression), and one normal prostate cell line (PNT2)...
March 19, 2018: Metabolites
https://www.readbyqxmd.com/read/29545650/solubility-of-the-proteinogenic-%C3%AE-amino-acids-in-water-ethanol-and-ethanol-water-mixtures
#10
Nathan A Bowden, Johan P M Sanders, Marieke E Bruins
The addition of organic solvents to α-amino acids in aqueous solution could be an effective method in crystallization. We reviewed the available data on the solubility of α-amino acids in water, water-ethanol mixtures, and ethanol at 298.15 K and 0.1 MPa. The solubility of l-alanine, l-proline, l-arginine, l-cysteine, and l-lysine in water and ethanol mixtures and the solubility of l-alanine, l-proline, l-arginine, l-cysteine, l-lysine, l-asparagine, l-glutamine, l-histidine, and l-leucine in pure ethanol systems were measured and are published here for the first time...
March 8, 2018: Journal of Chemical and Engineering Data
https://www.readbyqxmd.com/read/29536267/leucine-pd-loaded-5-5-single-walled-carbon-nanotube-matrix-as-a-novel-nanobiosensors-for-in-silico-detection-of-protein
#11
Mehdi Yoosefian, Nazanin Etminan
We have designed a novel nanobiosensor for in silico detecting proteins based on leucine/Pd-loaded single-walled carbon nanotube matrix. Density functional theory at the B3LYP/6-31G (d) level of theory was realized to analyze the geometrical and electronic structure of the proposed nanobiosensor. The solvent effects were investigated using the Tomasi's polarized continuum model. Atoms-in-molecules theory was used to study the nature of interactions by calculating the electron density ρ(r) and Laplacian at the bond critical points...
June 2018: Amino Acids
https://www.readbyqxmd.com/read/29524618/the-influence-of-surface-active-l-leucine-and-1-2-dipalmitoyl-sn-glycero-3-phosphatidylcholine-dppc-in-the-improvement-of-aerosolization-of-pyrazinamide-and-moxifloxacin-co-spray-dried-powders
#12
Basanth Babu Eedara, Bhamini Rangnekar, Colin Doyle, Alex Cavallaro, Shyamal C Das
Pharmacotherapy of tuberculosis is potentially more efficient when delivered by the inhaled route than by the current oral and/or parenteral routes due to the higher concentration of drug reaching the primary region of infection in the lungs. This study investigated the influence of the amino acid l-leucine alone and in combination with the phospholipid, 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), on the aerosolization behaviour of the anti-TB drugs, pyrazinamide and moxifloxacin HCl. Spray dried powders of pyrazinamide (P), moxifloxacin (M) alone and in combination with 10% l-leucine (PL and ML) and 10% DPPC (PLD and MLD) were produced...
May 5, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29523060/properties-of-bacterial-and-archaeal-branched-chain-amino-acid-aminotransferases
#13
REVIEW
E Yu Bezsudnova, K M Boyko, V O Popov
Branched-chain amino acid aminotransferases (BCATs) catalyze reversible stereoselective transamination of branched-chain amino acids (BCAAs) L-leucine, L-isoleucine, and L-valine. BCATs are the key enzymes of BCAA metabolism in all organisms. The catalysis proceeds through the ping-pong mechanism with the assistance of the cofactor pyridoxal 5'-phosphate (PLP). BCATs differ from other (S)-selective transaminases (TAs) in 3D-structure and organization of the PLP-binding domain. Unlike other (S)-selective TAs, BCATs belong to the PLP fold type IV and are characterized by the proton transfer on the re-face of PLP, in contrast to the si-specificity of proton transfer in fold type I (S)-selective TAs...
December 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/29492623/development-and-validation-of-a-rapid-selective-and-sensitive-lc-ms-ms-method-for-simultaneous-determination-of-d-and-l-amino-acids-in-human-serum-application-to-the-study-of-hepatocellular-carcinoma
#14
Minlu Han, Mengyu Xie, Jun Han, Daoyi Yuan, Tian Yang, Ying Xie
A validated liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of D- and L-amino acids in human serum. Under the optimum conditions, except for DL-proline, L-glutamine, and D-lysine, the enantioseparation of the other 19 enantiomeric pairs of proteinogenic amino acids and nonchiral glycine was achieved with a CROWNPAK CR-I(+) chiral column within 13 min. The lower limits of quantitation for L-amino acids (including glycine) and D-amino acids were 5-56.25 μM and 0...
April 2018: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/29488452/isovaleronitrile-co-induced-with-its-precursor-l-leucine-by-herbivory-in-the-common-evening-primrose-stimulates-foraging-behavior-of-the-predatory-blue-shield-bug
#15
Koji Noge, Shigeru Tamogami
Herbivore-induced plant volatiles play important roles in plant-insect and plant-plant interactions. The common evening primrose, Oenothera biennis, is often infested by the flea beetle, Altica oleracea, on which the predatory blue shield bug, Zicrona caerulea, is usually found. This observation suggests that the predatory bug can discriminate infested plants from intact ones to locate its prey. In this study, l-leucine-derived nitrogen-containing compounds [isovaleronitrile (3-methylbutanenitrile), (E/Z)-isovaleraldoxime and 3-methyl-1-nitrobutane] and some terpenes were identified as a characteristic volatile blend from herbivore-infested O...
March 2018: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/29486562/polymer-lipid-microparticles-for-pulmonary-delivery
#16
Georgios K Eleftheriadis, Melpomeni Akrivou, Nikolaos Bouropoulos, John Tsibouklis, Ioannis S Vizirianakis, Dimitrios G Fatouros
Toward engineering approaches that are designed to optimize the particle size, morphology, and mucoadhesion behavior of the particulate component of inhaler formulations, this paper presents the preparation, physicochemical characterization, and preliminary in vitro evaluation of multicomponent polymer-lipid systems that are based on "spray-drying engineered" α-lactose monohydrate microparticles. The formulations combine an active (budesonide) with a lung surfactant (dipalmitoylphosphatidylcholine) and with materials that are known for their desirable effects on morphology (polyvinyl alcohol), aerosolization (l-leucine), and mucoadhesion (chitosan)...
March 20, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29483542/understanding-the-high-l-valine-production-in-corynebacterium-glutamicum-vwb-1-using-transcriptomics-and-proteomics
#17
Hailing Zhang, Yanyan Li, Chenhui Wang, Xiaoyuan Wang
Toward the elucidation of the advanced mechanism of L-valine production by Corynebacterium glutamicum, a highly developed industrial strain VWB-1 was analyzed, employing the combination of transcriptomics and proteomics methods. The transcriptional level of 1155 genes and expression abundance of 96 proteins were changed significantly by the transcriptome and proteome comparison of VWB-1 and ATCC 13869. It was indicated that the key genes involved in the biosynthesis of L-valine, ilvBN, ilvC, ilvD, ilvE were up-regulated in VWB-1, which together made prominent contributions in improving the carbon flow towards L-valine...
February 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29467335/apolipoproteins-e-and-ciii-interact-to-regulate-hdl-metabolism-and-coronary-heart-disease-risk
#18
Allyson M Morton, Manja Koch, Carlos O Mendivil, Jeremy D Furtado, Anne Tjønneland, Kim Overvad, Liyun Wang, Majken K Jensen, Frank M Sacks
BACKGROUND: Subspecies of HDL contain apolipoprotein E (apoE) and/or apoCIII. Both proteins have properties that could affect HDL metabolism. The relation between HDL metabolism and risk of coronary heart disease (CHD) is not well understood. METHODS: Eighteen participants were given a bolus infusion of [D3]L-leucine to label endogenous proteins on HDL. HDL was separated into subspecies containing apoE and/or apoCIII and then into 4 sizes. Metabolic rates for apoA-I in HDL subspecies and sizes were determined by interactive modeling...
February 22, 2018: JCI Insight
https://www.readbyqxmd.com/read/29442259/lc-ms-based-serum-metabolomics-reveals-a-distinctive-signature-in-patients-with-rheumatoid-arthritis
#19
Ju Li, Nan Che, Lingxiao Xu, Qian Zhang, Qi Wang, Wenfeng Tan, Miaojia Zhang
Metabolomics has been applied to explore altered metabolite profiles in disease and identify unique metabolic signatures in recent years. We aim to characterize the metabolic profile of rheumatoid arthritis patients and explore its underlying pathological processes using metabolomics approach. Serum samples from 30 rheumatoid arthritis (RA) patients, 30 primary Sjogren's syndrome (pSS) patients, and 32 healthy controls (HC) were collected. The sample was analyzed by ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS)...
February 13, 2018: Clinical Rheumatology
https://www.readbyqxmd.com/read/29439854/rapid-sensing-of-l-leucine-by-human-and-murine-hypothalamic-neurons-neurochemical-and-mechanistic-insights
#20
Nicholas Heeley, Peter Kirwan, Tamana Darwish, Marion Arnaud, Mark L Evans, Florian T Merkle, Frank Reimann, Fiona M Gribble, Clemence Blouet
OBJECTIVE: Dietary proteins are sensed by hypothalamic neurons and strongly influence multiple aspects of metabolic health, including appetite, weight gain, and adiposity. However, little is known about the mechanisms by which hypothalamic neural circuits controlling behavior and metabolism sense protein availability. The aim of this study is to characterize how neurons from the mediobasal hypothalamus respond to a signal of protein availability: the amino acid l-leucine. METHODS: We used primary cultures of post-weaning murine mediobasal hypothalamic neurons, hypothalamic neurons derived from human induced pluripotent stem cells, and calcium imaging to characterize rapid neuronal responses to physiological changes in extracellular l-Leucine concentration...
April 2018: Molecular Metabolism
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