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American Journal of Health-system... Nov 2021
Topics: Acetamides; Humans; Imatinib Mesylate; Mesylates
PubMed: 34498057
DOI: 10.1093/ajhp/zxab335 -
Yakugaku Zasshi : Journal of the... 2021"Retinoid" is the general term for vitamin A derivatives and chemical compounds that act like vitamin A. Vitamin A are composed of four isoprene units and are named... (Review)
Review
"Retinoid" is the general term for vitamin A derivatives and chemical compounds that act like vitamin A. Vitamin A are composed of four isoprene units and are named according to their terminal functional group, such as retinol (OH, 1), retinal (CHO, 2), and retinoic acid (COH, 3). Vitamin A usually refers to retinol. In the past few decades, major advances in research on vitamin A have improved our understanding of its fundamental roles and physiological significance in living cells. In this review, three types of chemical biology studies using vitamin A analogs are described: (1) conformational studies of the chromophore in retinal proteins (rhodopsin, phoborhodopsin, and retinochrome), especially the conformation around the cyclohexene ring; (2) structure-activity relationship studies of retinoic acid analogs to create new signaling molecules for activating nuclear receptors; and (3) development of a new channelrhodopsin with an absorption maximum at longer wavelength to overcome the various demerits of channelrhodopsins used in optogenetics, as well as the stereoselective synthesis of retinoid isomers and their analogs using a diene-tricarbonyliron complex or a palladium-catalyzed cross-coupling reaction between vinyl triflates and stannyl olefins.
Topics: Alkenes; Catalysis; Channelrhodopsins; Cyclohexenes; Eye Proteins; Isomerism; Mesylates; Molecular Conformation; Nuclear Reactors; Palladium; Retinoids; Stereoisomerism; Structure-Activity Relationship; Vinyl Compounds; Vitamin A
PubMed: 33790122
DOI: 10.1248/yakushi.20-00230 -
Molecules (Basel, Switzerland) Jul 2020Superelectrophiles are reactive species that often carry multiple positive charges. They have been useful in numerous synthetic methods and they often exhibit highly... (Review)
Review
Superelectrophiles are reactive species that often carry multiple positive charges. They have been useful in numerous synthetic methods and they often exhibit highly unusual reactivities. Recent advances in superelectrophile chemistry are discussed in this review.
Topics: Aza Compounds; Cyclization; Electrochemistry; Mesylates; Quinolones
PubMed: 32707680
DOI: 10.3390/molecules25143281 -
Chemical Reviews Sep 2022Due to their solution processability and unique photoelectric characteristics, perovskite solar cells (PSCs) have shown considerable promise in the area of renewable... (Review)
Review
Due to their solution processability and unique photoelectric characteristics, perovskite solar cells (PSCs) have shown considerable promise in the area of renewable energy. Although their power conversion efficiency (PCE) has risen from 3.8% to 25.7% in only a few years, their short lifetime and high material prices continue to be key roadblocks to commercial viability. Charge transporting materials (CTMs), such as hole/electron transporting materials, are critical components in PSCs because they not only govern hole or electron extraction and transporting from the perovskite layer to the electrodes but also protect the perovskite from direct contact with the ambient environment. CTMs are split into two types: inorganic CTMs (ICTMs) and organic CTMs (OCTMs). Because of their inexpensive prices, well-adjusted energy levels, and low temperature solution-processed features, OCTMs have been more frequently explored and employed than ICTMs. Various forms of OCTMs with more straightforward synthetic pathways and better performance have been thoroughly researched. Recent achievements in the development of OCTMs will be discussed and evaluated on a molecular level in this study, which will include a systematic categorization of OCTMs based on molecular functionalization techniques. In order to achieve highly efficient and stable PSCs, we will present insights on the structure-property relationship in the design of OCTMs as well as device stability. We hope that this analysis will serve as a comprehensive reference to molecular design guidelines for various types of OCTMs, spurring greater research toward designing highly efficient and OCTMs for stable PSCs.
Topics: Calcium Compounds; Cyclohexanes; Mesylates; Oxides; Solar Energy; Titanium
PubMed: 36112746
DOI: 10.1021/acs.chemrev.2c00166 -
Science (New York, N.Y.) Nov 2021To date, it remains challenging to selectively migrate a carbonyl oxygen within a given molecular scaffold, especially to an adjacent carbon. In this work, we describe a...
To date, it remains challenging to selectively migrate a carbonyl oxygen within a given molecular scaffold, especially to an adjacent carbon. In this work, we describe a simple one- or two-pot protocol that transposes a ketone to the vicinal carbon. This approach first converts the ketone to the corresponding alkenyl triflate, which can then undergo the palladium- and norbornene-catalyzed regioselective α-amination and ipso-hydrogenation enabled by a bifunctional hydrogen and nitrogen donor. The resulting “transposed enamine” intermediate can subsequently be hydrolyzed to produce the 1,2-carbonyl–migrated product. This method allows rapid access to unusual bioactive analogs through late-stage functionalization.
Topics: Amination; Carbon; Catalysis; Chemistry, Pharmaceutical; Hydrogen; Hydrogenation; Ketones; Mesylates; Molecular Structure; Norbornanes; Oxygen; Palladium; Technology, Pharmaceutical
PubMed: 34735246
DOI: 10.1126/science.abl7854 -
Clinical Pharmacokinetics Jan 2021We aimed to review the pharmacokinetics (PK) of intravenous busulfan in paediatric patients, identify covariate factors influencing exposure, investigate evidence of... (Review)
Review
We aimed to review the pharmacokinetics (PK) of intravenous busulfan in paediatric patients, identify covariate factors influencing exposure, investigate evidence of changes in PK behaviour over time, and correlate exposure with efficacy and toxicity outcomes. A literature review was undertaken of original research published between 2007 and 2019, investigating the PK and pharmacodynamics (PD) of intravenous busulfan in patients ≤ 18 years of age. The review identified 41 publications characterising the PK, and 45 publications describing the PD, of busulfan. Median typical clearance (CL) was 0.22 L/h/kg and median typical volume of distribution was 0.69 L/kg. Patient weight, age, glutathione-S-transferase A1 (GSTA1) genotype and busulfan dosing day/time were the most commonly identified factors affecting CL. Of nine studies investigating changes in CL, seven reported reduced CL over the 4-day course of treatment. Exposure monitoring methods and therapeutic targets were heterogeneous across studies. Relationships between busulfan exposure and patient outcomes were observed in five studies. One study observed a cumulative area under the concentration-time curve over all days of treatment of between 78 and 101 mg/L·h, and two studies observed an average concentration at first dose of < 600 ng/mL improved overall survival, transplant-related mortality, or relapse. One study observed increased sinusoidal obstructive syndrome with maximum busulfan concentration > 1.88 ng/mL. Patient weight, age and GSTA1 genotype are important covariates to consider when individualising busulfan therapy. Reduced busulfan CL over time may need to be accounted for, particularly in patients not receiving phenytoin co-therapy. Standardised monitoring of busulfan exposure over the entire course of treatment and further investigation of the role of busulfan metabolites and pharmacogenomics is warranted.
Topics: Administration, Intravenous; Body Weight; Busulfan; Child; Genotype; Hematopoietic Stem Cell Transplantation; Humans
PubMed: 33128207
DOI: 10.1007/s40262-020-00947-2 -
Organic Letters Jun 2015Air- and moisture-stable N-trifluoromethylthio sulfoximines have been prepared from N-H-sulfoximines via the corresponding N-Br derivatives in excellent yields. The...
Air- and moisture-stable N-trifluoromethylthio sulfoximines have been prepared from N-H-sulfoximines via the corresponding N-Br derivatives in excellent yields. The two-step process starts with an easy-to-perform bromination at the sulfoximine nitrogen, followed by a reaction with silver trifluoromethanethiolate. A one-pot reaction sequence allows difficult to prepare products to be obtained.
Topics: Catalysis; Halogenation; Mesylates; Methionine Sulfoximine; Molecular Structure; Nitrogen; Stereoisomerism
PubMed: 26029817
DOI: 10.1021/acs.orglett.5b01384 -
MSphere Oct 2021Tannerella forsythia is a Gram-negative oral pathogen known to possess an O-glycosylation system responsible for targeting multiple proteins associated with virulence at...
Tannerella forsythia is a Gram-negative oral pathogen known to possess an O-glycosylation system responsible for targeting multiple proteins associated with virulence at the three-residue motif (D)(S/T)(A/I/L/V/M/T). Multiple proteins have been identified to be decorated with a decasaccharide glycan composed of a poorly defined core plus a partially characterized species-specific section. To date, glycosylation studies have focused mainly on the two S-layer glycoproteins, TfsA and TfsB, so the true extent of glycosylation within this species has not been fully explored. In the present study, we characterize the glycoproteome of by employing FAIMS-based glycopeptide enrichment of a cell membrane fraction. We demonstrate that at least 13 glycans are utilized within the glycoproteome, varying with respect to the presence of the three terminal sugars and the presence of fucose and digitoxose residues at the reducing end. To improve the localization of glycosylation events and enhance the detection of glycopeptides, we utilized trifluoromethanesulfonic acid treatment to allow the selective chemical cleavage of glycans. Reducing the chemical complexity of glycopeptides dramatically improved the number of glycopeptides identified and our ability to localize glycosylation sites by ETD fragmentation, leading to the identification of 312 putative glycosylation sites in 145 glycoproteins. Glycosylation site analysis revealed that glycosylation occurs on a much broader motif than initially reported, with glycosylation found at (D)(S/T)(A/I/L/V/M/T/S/C/G/F). The prevalence of this broader glycosylation motif in the genome suggests the existence of hundreds of potential O-glycoproteins in this organism. Tannerella forsythia is an oral pathogen associated with severe forms of periodontal disease characterized by destruction of the tooth's supporting tissues, including the bone. The bacterium releases a variety of proteins associated with virulence on the surface of outer membrane vesicles. There is evidence that these proteins are modified by glycosylation, and this modification is essential for virulence in producing disease. We have utilized novel techniques coupled with mass spectrometry to identify over 13 glycans and 312 putative glycosylation sites in 145 glycoproteins within . Glycosylation site analysis revealed that this modification occurs on a much broader motif than initially reported such that there is a high prevalence of potential glycoproteins in this organism that may help to explain its role in periodontal disease.
Topics: Bacterial Proteins; Glycoproteins; Glycosylation; Mass Spectrometry; Membrane Glycoproteins; Mesylates; Protein Transport; Proteome; Tannerella forsythia; Virulence
PubMed: 34523981
DOI: 10.1128/mSphere.00649-21 -
Journal of Applied Physiology... Aug 2021Sepsis-induced diaphragm dysfunction is a major contributor to respiratory failure in mechanically ventilated patients. There are no pharmacological treatments for this...
Sepsis-induced diaphragm dysfunction is a major contributor to respiratory failure in mechanically ventilated patients. There are no pharmacological treatments for this syndrome, but studies suggest that diaphragm weakness is linked to mitochondrial free radical generation. We hypothesized that administration of mitoquinone mesylate (MitoQ), a mitochondrially targeted free radical scavenger, would prevent sepsis-induced diaphragm dysfunction. We compared diaphragm function in 4 groups of male mice: ) sham-operated controls treated with saline (0.3 mL ip), ) sham-operated treated with MitoQ (3.5 mg/kg/day given intraperitoneally in saline), ) cecal ligation puncture (CLP) mice treated with saline, and ) CLP mice treated with MitoQ. Forty-eight hours after surgery, we assessed diaphragm force generation, myosin heavy chain content, state 3 mitochondrial oxygen consumption (OCR), and aconitase activity. We also determined effects of MitoQ in female mice with CLP sepsis and in mice with endotoxin-induced sepsis. CLP decreased diaphragm specific force generation and MitoQ prevented these decrements (e.g. maximal force averaged 30.2 ± 1.3, 28.0 ± 1.3, 12.8 ± 1.9, and 30.0 ± 1.0 N/cm for sham, sham + MitoQ, CLP, and CLP + MitoQ groups, respectively, < 0.001). CLP also reduced diaphragm mitochondrial OCR and aconitase activity; MitoQ blocked both effects. Similar responses were observed in female mice and in endotoxin-induced sepsis. Moreover, delayed MitoQ treatment (by 6 h) was as effective as immediate treatment. These data indicate that MitoQ prevents sepsis-induced diaphragm dysfunction, preserving force generation. MitoQ may be a useful therapeutic agent to preserve diaphragm function in critically ill patients with sepsis. This is the first study to show that mitoquinone mesylate (MitoQ), a mitochondrially targeted antioxidant, treats sepsis-induced skeletal muscle dysfunction. This biopharmaceutical agent is without known side effects and is currently being used by healthy individuals and in clinical trials in patients with various diseases. When taken together, our results suggest that MitoQ has the potential to be immediately translated into treatment for sepsis-induced skeletal muscle dysfunction.
Topics: Animals; Diaphragm; Female; Humans; Male; Mesylates; Mice; Organophosphorus Compounds; Sepsis; Ubiquinone
PubMed: 34197233
DOI: 10.1152/japplphysiol.01053.2020 -
British Journal of Haematology Nov 2021
Topics: Busulfan; Humans; Transplantation Conditioning; Transplantation, Homologous
PubMed: 34514593
DOI: 10.1111/bjh.17816