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Antiviral Research Oct 2018Influenza continues to pose a threat to public health by causing illness and mortality in humans. Discovering host factors that regulate influenza virus propagation is...
Influenza continues to pose a threat to public health by causing illness and mortality in humans. Discovering host factors that regulate influenza virus propagation is vital for the development of novel drugs. We have previously reported that sphingosine kinase (SphK) 1 promotes influenza A virus (IAV) replication in vitro. Here we demonstrate that the other isoform of SphK, SphK2 promotes the replication of influenza A virus (IAV) in cultured cells, and temporary inhibition of SphK1 or SphK2 enhances the host defense against influenza in mice. IAV infection led to an increased expression and phosphorylation of SphK2 in host cells. Furthermore, pharmacologic inhibition or siRNA-based knockdown of SphK2 attenuated IAV replication in vitro. Notably, oral administration of an SphK2-specific inhibitor substantially improved the viability of mice following IAV infection. In addition, the local instillation of an SphK1-specific inhibitor or an inhibitor that globally blocks SphK1 and SphK2 provided protection to IAV-infected mice. Collectively, our results indicate that both SphK1 and SphK2 function as proviral factors during IAV infection in vivo. Therefore, SphK1 and SphK2 represent potential host targets for therapeutics against influenza.
Topics: A549 Cells; Adamantane; Administration, Oral; Amino Alcohols; Aminophenols; Animals; Cell Line; Disease Models, Animal; Female; Gene Knockdown Techniques; HEK293 Cells; Humans; Influenza A virus; Mice; Mice, Inbred C57BL; Orthomyxoviridae Infections; Phosphorylation; Phosphotransferases (Alcohol Group Acceptor); Protein Isoforms; Pyridines; RNA, Small Interfering; Sphingosine; Thiazoles; Virus Replication
PubMed: 30125617
DOI: 10.1016/j.antiviral.2018.08.010 -
The Journal of Biological Chemistry Aug 1954
Topics: Amino Alcohols; Histidine; Histidinol
PubMed: 13192138
DOI: No ID Found -
International Journal of Molecular... May 2024The chiral H-BINOL derivatives R- and R- were efficiently synthesized via a Suzuki coupling reaction, and they can be used as novel dialdehyde fluorescent probes for the...
The chiral H-BINOL derivatives R- and R- were efficiently synthesized via a Suzuki coupling reaction, and they can be used as novel dialdehyde fluorescent probes for the enantioselective recognition of R/S-2-amino-1-phenylethanol. In addition, R- is much more effective than R-. Scanning electron microscope images and X-ray analyses show that R- can form supramolecular vesicles through the self-assembly effect of the π-π force and strong hydrogen bonding. As determined via analysis, the fluorescence of the probe was significantly enhanced by mixing a small amount of S-2-amino-1-phenylethanol into R-, with a redshift of 38 nm, whereas no significant fluorescence response was observed in R-2-amino-1-phenylethanol. The enantioselective identification of S-2-amino-1-phenylethanol by the probe R- was further investigated through nuclear magnetic titration and fluorescence kinetic experiments and DFT calculations. The results showed that this mechanism was not only a simple reactive probe but also realized object recognition through an ICT mechanism. As the intramolecular hydrogen bond activated the carbonyl group on the probe R-, the carbonyl carbon atom became positively charged. As a strong nucleophile, the amino group of S-2-amino-1-phenylethanol first transferred the amino electrons to a carbonyl carbocation, resulting in a significantly enhanced fluorescence of the probe R- and a 38 nm redshift. Similarly, S-2-amino-1-phenylethanol alone caused severe damage to the self-assembled vesicle structure of the probe molecule itself due to its spatial structure, which made R- highly enantioselective towards it.
Topics: Stereoisomerism; Amino Alcohols; Hydrogen Bonding; Fluorescent Dyes; Kinetics; Molecular Structure; Models, Molecular; Naphthols
PubMed: 38891794
DOI: 10.3390/ijms25115606 -
Journal of the American Chemical Society Jun 2019We report the development of a Pd(II)/(±)-MeO-SOX/2,5-dimethylbenzoquinone system that enables unprecedented access to anti-1,3 amino alcohol motifs in good yields (33...
We report the development of a Pd(II)/(±)-MeO-SOX/2,5-dimethylbenzoquinone system that enables unprecedented access to anti-1,3 amino alcohol motifs in good yields (33 substrates, avg. 66% isolated yield, >20:1 dr) and high selectivities (avg. 10:1 dr). Switching ligands to (±)-CF-SOX with the use of a less bulky quinone oxidant, the kinetic syn-1,3 amino alcohol motif can be accessed in comparable yields and selectivities. Advantages of the stereodivergent nature of this reaction are seen in the synthesis of anti- and syn-1,3 amino alcohol vitamin D3 analogue intermediates in half the steps and higher overall yield relative to previous routes. Additionally, all eight possible stereoisomers of a chiral diamino alcohol core are generated from two amino acids. Mechanistic studies reveal that the anti-isomer is furnished through concurrent Pd(II)(SOX) catalyzed C-H amination and Pd(0)(SOX) catalyzed isomerization cycles.
Topics: Alkenes; Amino Alcohols; Benzoquinones; Catalysis; Organoplatinum Compounds; Oxazines; Stereoisomerism; Sulfoxides
PubMed: 31140795
DOI: 10.1021/jacs.9b02690 -
Proceedings of the National Academy of... Feb 1973The oligopeptide permease of Escherichia coli has been characterized by Payne, Gilvarg, and their colleagues. We have confirmed its existence in Salmonella typhimurium,...
The oligopeptide permease of Escherichia coli has been characterized by Payne, Gilvarg, and their colleagues. We have confirmed its existence in Salmonella typhimurium, and have isolated a series of mutants lacking the permease. We use this transport system for smuggling a histidine biosynthetic intermediate, histidinol phosphate ester, into the bacteria as its glycylglycyl derivative, Gly-Gly-histidinol phosphate. Free histidinol phosphate ester is not transported into Salmonella. Several amino-acid analogues are shown to be much more inhibitory to Salmonella when presented to the bacteria in the form of tripeptides than as the free amino acids. The implications of this work for practical purposes are discussed. The synthesis of Gly-Gly-histidinol phosphate is described.
Topics: Amino Alcohols; Biological Transport; Ethionine; Glycine; Histidine; Imidazoles; Membrane Transport Proteins; Mutation; Norleucine; Oligopeptides; Organophosphorus Compounds; Salmonella typhimurium
PubMed: 4568730
DOI: 10.1073/pnas.70.2.456 -
International Journal of Molecular... Oct 2021Acid phosphatase and its regulation are important objects of biological and clinical research and play an important role in the development and treatment of prostate and...
BACKGROUND
Acid phosphatase and its regulation are important objects of biological and clinical research and play an important role in the development and treatment of prostate and bone diseases. The newly patented aminoalkanol (4-[2-hydroxy-3-(propan-2-ylamino)propyl]-1,7-dimethyl-8,9-diphenyl-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5,10-trione hydrochloride) (I) and (4-[3-(dimethylamino)-2-hydroxypropyl]-1,7-dimethyl-8,9-diphenyl-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5,10-trione hydrochloride) (II) derivatives have potential anticancer activity, and their influence on enzymatic activity can significantly impact the therapeutic effects of acid phosphatase against many diseases. Therefore, in this study, we investigated the action of compounds (I) and (II) on acid phosphatase.
METHODS
Capillary electrophoresis was used to evaluate the inhibition of acid phosphatase. Lineweaver-Burk plots were constructed to compare the Km of this enzyme in the presence of inhibitors (I) or (II) with the Km in solutions without these inhibitors.
RESULTS
Compound (I) showed a stronger competitive inhibition against acid phosphatase, whereas derivative (II) showed a weaker competitive type of inhibition. The detailed kinetic studies of these compounds showed that their type and strength of inhibition as well as affinity depend on the kind of substituent occurring in the main chemical molecule.
CONCLUSIONS
This study is of great importance because the disclosed inhibition of acid phosphatase by compounds (I) and (II) raises the question of whether these compounds could have any effect on the treatment possibilities of prostate diseases.
Topics: Acid Phosphatase; Amino Alcohols; Antineoplastic Agents; Drug Discovery; Enzyme Inhibitors; Humans; Kinetics; Male; Molecular Docking Simulation; Prostate
PubMed: 34769193
DOI: 10.3390/ijms222111761 -
PloS One 2017Aminoalcohols have been addressed as activating buffers for alkaline phosphatase. However, there is no record on the buffer activation regarding organophosphorus...
Aminoalcohols have been addressed as activating buffers for alkaline phosphatase. However, there is no record on the buffer activation regarding organophosphorus hydrolase (OPH). Here we reported the activating effects of aminoalcohols on OPH-catalyzed hydrolysis of diisopropylfluorophosphate (DFP), an analog molecule of G-type warfare agents. The kinetic parametors kcat, Vmax and kcat/Km in the OPH reaction were remarkably increased in the buffers (pH 8.0, 25°C) containing aminoalcohols with C2 between nitrogen (N) and oxygen (O) in their structures, including triethanolamine (TEA), diethanolamine, monoethanolamine, 1-amino-2-propanol, 2-amino-2-methyl-1-propanol, and triisopropanolamine. In contrast, much lower or no rate-enhancing effects were observed in the adding of amines, alcohols, amine/alcohol mixtures, or 3-amino-1-propanol (C3 between N and O). The 300 mM TEA further increased DFP-degrading activities of OPH mutants F132Y and L140Y, the previously reported OPH mutants with desirable activities towards DFP. However, the treatment of ethylenediaminetetraacetate (EDTA) markedly abolished the TEA-induced activation of OPH. The product fluoride effectively inhibited OPH-catalyzed hydrolysis of DFP by a linear mixed inhibition (inhibition constant Ki ~ 3.21 mM), which was partially released by TEA adding at initial or later reaction stage. The obtained results indicate the activation of OPH by aminoalcohol buffers could be attributed to the reduction of fluoride inhibition, which would be beneficial to the hydrolase-based detoxification of organophosphofluoridate.
Topics: Amino Alcohols; Aryldialkylphosphatase; Enzyme Activation; Hydrolysis; Isoflurophate; Kinetics; Sphingobacterium; Substrate Specificity
PubMed: 28085964
DOI: 10.1371/journal.pone.0169937 -
The Journal of Organic Chemistry Feb 2015The hydroxyamination reagent Br-N-(CO2Me)2 underwent Markovnikov addition to various olefins in the presence of catalytic BF3·OEt2 and provides efficient access to...
The hydroxyamination reagent Br-N-(CO2Me)2 underwent Markovnikov addition to various olefins in the presence of catalytic BF3·OEt2 and provides efficient access to aminoalcohols. The reaction provided the trans-1-bromo, 2-N-bis-carbamate adduct stereoisomer in all cases. The resulting adduct underwent cyclization to give an oxazolidinone, which could be readily hydrolyzed to an oxazolidin-2-one or an amino alcohol.
Topics: Alkenes; Amination; Amino Alcohols; Carbamates; Catalysis; Cyclization; Indicators and Reagents; Magnetic Resonance Spectroscopy; Oxazolidinones; Stereoisomerism
PubMed: 25574949
DOI: 10.1021/jo502369d -
Journal of the American Chemical Society Jun 2007
Regio- and stereoselective cross-coupling of substituted olefins and imines. A convergent stereoselective synthesis of saturated 1,5-amino-alcohols and substituted piperidines.
Topics: Alkenes; Amino Alcohols; Imines; Molecular Biology; Piperidines
PubMed: 17530760
DOI: 10.1021/ja071974v -
Bioorganic & Medicinal Chemistry Oct 2017We report short and efficient scalable syntheses of enantiomerically pure (3R,4S)-3-(hydroxymethyl4-(hydroxyethyl))-piperidine and...
We report short and efficient scalable syntheses of enantiomerically pure (3R,4S)-3-(hydroxymethyl4-(hydroxyethyl))-piperidine and 1-hydroxymethyl-octahydro-1H-pyrano[3,4-c]pyridine scaffolds. The alkaloid core was readily synthesized from naturally occurring quinine and can serve as a valued starting point for drug-discovery. Cleavage of a terminal 1,2-diol and acid catalysed epoxide opening cyclization are the key steps involved. A number of members of a projected small-molecular library is synthesized for each scaffold.
Topics: Amino Alcohols; Chemistry Techniques, Synthetic; Drug Discovery; Piperidines; Pyridines; Quinine; Small Molecule Libraries
PubMed: 28720326
DOI: 10.1016/j.bmc.2017.07.016