scholarly journals Racemization-free synthesis of Nα-2-thiophenoyl-phenylalanine-2-morpholinoanilide enantiomers and their antimycobacterial activity

Amino Acids ◽  
2021 ◽  
Author(s):  
Lea Mann ◽  
Markus Lang ◽  
Philipp Schulze ◽  
Jan Henrik Halz ◽  
René Csuk ◽  
...  
Keyword(s):  
Title Compound ◽  
Mammalian Cells ◽  
Antimycobacterial Activity ◽  
Lead Compound ◽  
Coupling Reagents ◽  
Hydrogen Bonding Interactions ◽  
Amide Coupling ◽  
Subsequent Separation ◽  
Synthetic Routes ◽  
Insight Into

AbstractNα-2-thiophenoyl-d-phenylalanine-2-morpholinoanilide (MMV688845, IUPAC: N-(1-((2-morpholinophenyl)amino)-1-oxo-3-phenylpropan-2-yl)thiophene-2-carboxamide) from the Pathogen Box® library (Medicines for Malaria Ventures, MMV) is a promising lead compound for antimycobacterial drug development. Two straightforward synthetic routes to the title compound starting from phenylalanine or its Boc-protected derivative are reported. Employing Boc-phenylalanine as starting material and the T3P® and PyBOP® amide coupling reagents enables racemization-free synthesis, avoiding the need for subsequent separation of the enantiomers. The crystal structure of the racemic counterpart gives insight into the molecular structure and hydrogen bonding interactions in the solid state. The R-enantiomer of the title compound (derived from d-phenylalanine) exhibits activity against non-pathogenic and pathogenic mycobacterial strains, whereas the S-enantiomer is inactive. Neither of the enantiomers and the racemate of the title compound shows cytotoxicity against various mammalian cells.

2,4,6-Trimethylpyridine-3,5-dicarbonitrile

2006 ◽  
Vol 62 (7) ◽  
pp. o2765-o2767
Author(s):  
Hong-Li Wang ◽  
Bin Zhang ◽  
Yi Dai
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bonding ◽  
Title Compound ◽  
Asymmetric Unit ◽  
Compound C ◽  
Hydrogen Bonding Interactions

The title compound, C10H9N3, is essently planar, except for the methyl H atoms. The asymmetric unit consists of two molecules. In the crystal structure, weak intramolecular C—H...N hydrogen-bonding interactions occur, linking the molecules into chains propagating along the a axis.

scholarly journals The intracellular dynamic of protein palmitoylation

2010 ◽  
Vol 191 (7) ◽  
pp. 1229-1238 ◽  
Author(s):  
Christine Salaun ◽  
Jennifer Greaves ◽  
Luke H. Chamberlain
Keyword(s):  
Posttranslational Modifications ◽  
Posttranslational Modification ◽  
Mammalian Cells ◽  
Protein Functionality ◽  
Peripheral Membrane Proteins ◽  
Protein Palmitoylation ◽  
Thioester Bond ◽  
Intracellular Sorting ◽  
Intracellular Dynamic ◽  
Insight Into

S-palmitoylation describes the reversible attachment of fatty acids (predominantly palmitate) onto cysteine residues via a labile thioester bond. This posttranslational modification impacts protein functionality by regulating membrane interactions, intracellular sorting, stability, and membrane micropatterning. Several recent findings have provided a tantalizing insight into the regulation and spatiotemporal dynamics of protein palmitoylation. In mammalian cells, the Golgi has emerged as a possible super-reaction center for the palmitoylation of peripheral membrane proteins, whereas palmitoylation reactions on post-Golgi compartments contribute to the regulation of specific substrates. In addition to palmitoylating and depalmitoylating enzymes, intracellular palmitoylation dynamics may also be controlled through interplay with distinct posttranslational modifications, such as phosphorylation and nitrosylation.

scholarly journals Crystal structure of guanidinium hexafluoridovanadate(III), (CN3H6)3[VF6]: an unusual hybrid compound related to perovskite

2017 ◽  
Vol 73 (3) ◽  
pp. 244-246 ◽  
Author(s):  
Cameron Black ◽  
Philip Lightfoot
Keyword(s):  
Crystal Structure ◽  
Physical Properties ◽  
Title Compound ◽  
Crystal Chemical ◽  
Hybrid Compound ◽  
Structure Space ◽  
Perovskite Materials ◽  
Synthetic Routes ◽  
Cubic Structure ◽  
Covalent Interactions

Vanadium fluorides with novel crystal–chemical features and interesting physical properties can be prepared by solvothermal synthetic routes. The title compound, guanidinium hexafluoridovanadate(III), has a cubic structure (space group Pa\overline{3}), exhibiting isolated regular VF6 octahedral units, which are hydrogen bonded to protonated guanidinium moieties. Although the VF6 octahedral units are not linked directly together, there are structural similarities between this crystal structure and those of the wider family of perovskite materials, in particular, hybrid perovskites based on extended ligands such as cyanide. In this context, the octahedral tilt system of the present compound is of interest and demonstrates that unusual tilt systems can be mediated via `molecular' linkers which allow only supramolecular rather than covalent interactions.

scholarly journals 1,4a,7-Trimethyl-7-vinyl-1,2,3,4,4a,4b,5,6,7,8,10,10a-dodecahydrophenanthrene-1-carboxylic acid

2009 ◽  
Vol 65 (6) ◽  
pp. o1429-o1429
Author(s):  
Zhen-Dong Zhao ◽  
Yu-Xiang Chen ◽  
Yu-Min Wang ◽  
Liang-Wu Bi
Keyword(s):  
Hydrogen Bonding ◽  
Carboxylic Acid ◽  
Hydrogen Bonds ◽  
Title Compound ◽  
Molecular Conformation ◽  
Slash Pine ◽  
Carboxyl Groups ◽  
Isopimaric Acid ◽  
Hydrogen Bonding Interactions ◽  
Cyclohexene Ring

The title compound, also known as isopimaric acid, C20H30O2, was isolated from slash pine rosin. There are two unique molecules in the unit cell. The two cyclohexane rings have classical chair conformations. The cyclohexene ring represents a semi-chair. The molecular conformation is stabilized by weak intramolecular C—H...O hydrogen-bonding interactions. The molecules are dimerized through their carboxyl groups by O—H...O hydrogen bonds, formingR22(8) rings.

scholarly journals Bis(nitrilotriacetamide-κ4 N,O,O′,O′′)silver(I) nitrate

IUCrData ◽  
2018 ◽  
Vol 3 (1) ◽  
Author(s):  
Min Ren ◽  
Ming Yue ◽  
Jingwen Ran
Keyword(s):  
Hydrogen Bonding ◽  
Network Structure ◽  
Title Compound ◽  
Three Dimensional ◽  
Hydrogen Bonding Interactions ◽  
Dimensional Network

In the centrosymmetric cation of the title compound, [Ag(C6H12N4O3)2]NO3, the AgI ion, lying on a threefold rotoinversion axis, is coordinated by two N atoms and six O atoms from two nitrilotriacetamide ligands, forming a distorted dodecahedral environment. In the crystal, cations and anions are linked through N—H...O hydrogen-bonding interactions, leading to a three-dimensional network structure.

scholarly journals Ambroxol Induces Autophagy and Potentiates Rifampin Antimycobacterial Activity

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Seong Won Choi ◽  
Yuexi Gu ◽  
Ryan Scott Peters ◽  
Padmini Salgame ◽  
Jerrold J. Ellner ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Antimycobacterial Activity ◽  
Lead Compound ◽  
Content Type ◽  
Tuberculosis Model

ABSTRACT Host-directed therapy in tuberculosis is a potential adjunct to antibiotic chemotherapy directed at Mycobacterium tuberculosis. Ambroxol, a lead compound, emerged from a screen for autophagy-inducing drugs. At clinically relevant doses, ambroxol induced autophagy in vitro and in vivo and promoted mycobacterial killing in macrophages. Ambroxol also potentiated rifampin activity in a murine tuberculosis model.

scholarly journals Crystal structure of bis(μ2-4-tert-butyl-2-formylphenolato)-1:2κ3O1,O2:O1;3:4κ3O1,O2:O1-bis(4-tert-butyl-2-formylphenolato)-2κ2O1,O2;4κ2O1,O2-di-μ3-methoxido-1:2:3κ3O;1:3:4κ3O-di-μ2-methoxido-1:4κ2O;2:3κ2O-tetracopper(II)

2015 ◽  
Vol 71 (3) ◽  
pp. 324-326
Author(s):  
Bernhard Eberhard Christian Bugenhagen ◽  
Marc Heinrich Prosenc
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bonding ◽  
Coordination Sphere ◽  
Title Compound ◽  
Coordination Environment ◽  
Dinuclear Copper ◽  
Tert Butyl ◽  
Hydrogen Bonding Interactions ◽  
Square Planar

The structure of the title compound, [Cu4(CH3O)4(C11H13O2)4], consists of dimeric dinuclear copper(II) complexes oriented around a centre of inversion. Within each dinuclear fragment, the two CuIIatoms are in a distorted square-planar coordination sphere. Two neighbouring fragments are linked by four apical Cu—O contacts, yielding an overall square-pyramidal coordination environment for each of the four CuIIatoms. The molecules are arranged in layers parallel to (101). Non-classical C—H...O hydrogen-bonding interactions are observed between the layers.

Chemical carcinogens

2019 ◽  
pp. 79-90
Author(s):  
David H. Phillips
Keyword(s):  
Dna Repair ◽  
Cancer Incidence ◽  
Mammalian Cells ◽  
Human Exposure ◽  
Chemical Carcinogens ◽  
Regulatory Processes ◽  
Genotoxic Carcinogens ◽  
The Many ◽  
Transformation Methods ◽  
Insight Into

Large geographical and temporal differences in cancer incidence indicate that the causes of the majority of cases are a consequence of environmental and lifestyle factors. While many of these remain unknown, around half have known causes, and these include chemicals in air, water, and food, as well as products of industrial processes and of combustion. The major classes of chemical carcinogens and how they were discovered are described. A property shared by many of them is that they, or one or more of their metabolites, are electrophiles that can damage DNA in mammalian cells, leading to cellular responses including DNA repair, cytotoxicity, apoptosis, mutagenesis, and malignant transformation. Methods for predicting the carcinogenicity of new chemicals are part of the regulatory processes for safety assessment, and sensitive methods for monitoring human exposure to carcinogens provide insight into the aetiology of cancer. The mutational signatures that genotoxic carcinogens leave in the tumours they induce provide evidence of the chemicals that have caused them, and the approach has promise for shedding light on the many as-yet-unidentified cases of cancer worldwide.

scholarly journals Role for ribosome-associated quality control in sampling proteins for MHC class I-mediated antigen presentation

2020 ◽  
Vol 117 (8) ◽  
pp. 4099-4108 ◽  
Author(s):  
Débora Broch Trentini ◽  
Matteo Pecoraro ◽  
Shivani Tiwary ◽  
Jürgen Cox ◽  
Matthias Mann ◽  
...  
Keyword(s):  
Quality Control ◽  
Antigen Presentation ◽  
Mammalian Cells ◽  
Adaptive Immune System ◽  
Messenger Rnas ◽  
Mhc I ◽  
Adaptive Immune ◽  
Ribosome Stalling ◽  
Endogenous Substrates ◽  
Insight Into

Mammalian cells present a fingerprint of their proteome to the adaptive immune system through the display of endogenous peptides on MHC-I complexes. MHC-I−bound peptides originate from protein degradation by the proteasome, suggesting that stably folded, long-lived proteins could evade monitoring. Here, we investigate the role in antigen presentation of the ribosome-associated quality control (RQC) pathway for the degradation of nascent polypeptides that are encoded by defective messenger RNAs and undergo stalling at the ribosome during translation. We find that degradation of model proteins by RQC results in efficient MHC-I presentation, independent of their intrinsic folding properties. Quantitative profiling of MHC-I peptides in wild-type and RQC-deficient cells by mass spectrometry showed that RQC substantially contributes to the composition of the immunopeptidome. Our results also identify endogenous substrates of the RQC pathway in human cells and provide insight into common principles causing ribosome stalling under physiological conditions.

scholarly journals Deconstructing and repurposing the light-regulated interplay between Arabidopsis phytochromes and interacting factors

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
David Golonka ◽  
Patrick Fischbach ◽  
Siddhartha G. Jena ◽  
Julius R. W. Kleeberg ◽  
Lars-Oliver Essen ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Red Light ◽  
Interaction Data ◽  
Phytochrome B ◽  
Adaptive Responses ◽  
Membrane Recruitment ◽  
C Terminus ◽  
Regulated Gene Expression ◽  
Insight Into ◽  
Differential Affinity

AbstractPhytochrome photoreceptors mediate adaptive responses of plants to red and far-red light. These responses generally entail light-regulated association between phytochromes and other proteins, among them the phytochrome-interacting factors (PIF). The interaction with Arabidopsis thaliana phytochrome B (AtPhyB) localizes to the bipartite APB motif of the A. thaliana PIFs (AtPIF). To address a dearth of quantitative interaction data, we construct and analyze numerous AtPIF3/6 variants. Red-light-activated binding is predominantly mediated by the APB N-terminus, whereas the C-terminus modulates binding and underlies the differential affinity of AtPIF3 and AtPIF6. We identify AtPIF variants of reduced size, monomeric or homodimeric state, and with AtPhyB affinities between 10 and 700 nM. Optogenetically deployed in mammalian cells, the AtPIF variants drive light-regulated gene expression and membrane recruitment, in certain cases reducing basal activity and enhancing regulatory response. Moreover, our results provide hitherto unavailable quantitative insight into the AtPhyB:AtPIF interaction underpinning vital light-dependent responses in plants.

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