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The Plant Cell Oct 2019
Topics: Basic Helix-Loop-Helix Transcription Factors; Cyclopentanes; Diazonium Compounds; Marchantia; Oxylipins; Pyridines
PubMed: 31416824
DOI: 10.1105/tpc.19.00600 -
Organic Letters May 2017A metal-free synthesis of aryl bromides and iodides from anilines via halogen abstraction from bromotrichloromethane and diiodomethane is described. This one-pot...
A metal-free synthesis of aryl bromides and iodides from anilines via halogen abstraction from bromotrichloromethane and diiodomethane is described. This one-pot reaction affords aryl halides from the corresponding anilines in moderate to excellent yields without isolation of diazonium salts. The transformation has short reaction times, a simple workup, and insensitivity to moisture and air and avoids excess halogenation. DFT calculations support a S1 mechanism. This method represents a convenient alternative to the classic Sandmeyer reaction.
Topics: Aniline Compounds; Bromides; Catalysis; Iodides; Metals; Molecular Structure
PubMed: 28481557
DOI: 10.1021/acs.orglett.7b00771 -
Journal of the American Society of... Oct 2022Barlow's mitral valve disease with late systolic mitral regurgitation provides diagnostic and therapeutic challenges. The mechanisms of the regurgitation are still...
OBJECTIVES
Barlow's mitral valve disease with late systolic mitral regurgitation provides diagnostic and therapeutic challenges. The mechanisms of the regurgitation are still unclear. We hypothesized that the onset and the severity of late systolic regurgitation are determined by annulus dynamics and the mechanical stresses imposed by the left ventricle.
METHODS
Ten patients with Barlow's mitral valve disease and mitral annulus disjunction (MAD) were compared with 10 healthy controls. Resting blood pressure was measured, and transthoracic three-dimensional echocardiography was analyzed using a holographic display that allows tracking and measurements of mitral annulus surface area (ASA) throughout the cardiac cycle. A novel annulus elastance index (dASA/dP) was calculated between aortic valve opening and onset of mitral regurgitation. Severity of MAD was quantified as the disjunction index (mm × degree). Leaflet coaptation area was calculated using a finite element model.
RESULTS
Peak systolic ASAs in controls and patients were 9.3 ± 0.6 and 21.1 ± 3.1 cm, respectively (P < .001). In patients, the ASA increased rapidly during left ventricular ejection, and onset of mitral regurgitation coincided closely with peak upslope of annulus area change (dASA/dt). The finite element model showed a close association between rapid annulus displacement and coaptation area deficit in Barlow's mitral valve disease. Systolic annulus elastance index (0.058 ± 0.036 cm/mm Hg) correlated strongly with disjunction index (r = 0.91, P < .0001). Moreover, regurgitation volume showed a positive correlation with systolic blood pressure (r = 0.80, P < .01).
CONCLUSION
The present pilot study supports the hypothesis that annulus dilatation may accentuate mitral valve regurgitation in patients with Barlow's mitral valve disease. A novel annulus elastance index may predict the severity of mitral valve regurgitation in selected patients.
Topics: Diazonium Compounds; Elasticity; Humans; Mitral Valve; Mitral Valve Insufficiency; Mitral Valve Prolapse; Pilot Projects; Sulfanilic Acids
PubMed: 35842077
DOI: 10.1016/j.echo.2022.07.001 -
Nature Microbiology Dec 2019Bacterial autotrophs often rely on CO concentrating mechanisms (CCMs) to assimilate carbon. Although many CCM proteins have been identified, a systematic screen of the...
Bacterial autotrophs often rely on CO concentrating mechanisms (CCMs) to assimilate carbon. Although many CCM proteins have been identified, a systematic screen of the components of CCMs is lacking. Here, we performed a genome-wide barcoded transposon screen to identify essential and CCM-related genes in the γ-proteobacterium Halothiobacillus neapolitanus. Screening revealed that the CCM comprises at least 17 and probably no more than 25 genes, most of which are encoded in 3 operons. Two of these operons (DAB1 and DAB2) contain a two-gene locus that encodes a domain of unknown function (Pfam: PF10070) and a putative cation transporter (Pfam: PF00361). Physiological and biochemical assays demonstrated that these proteins-which we name DabA and DabB, for DABs accumulate bicarbonate-assemble into a heterodimeric complex, which contains a putative β-carbonic anhydrase-like active site and functions as an energy-coupled inorganic carbon (C) pump. Interestingly, DAB operons are found in a diverse range of bacteria and archaea. We demonstrate that functional DABs are present in the human pathogens Bacillus anthracis and Vibrio cholerae. On the basis of these results, we propose that DABs constitute a class of energized C pumps and play a critical role in the metabolism of C throughout prokaryotic phyla.
Topics: Archaea; Bacillus anthracis; Bacteria; Bacterial Proteins; Carbon; Carbon Dioxide; Carbonic Anhydrases; Carrier Proteins; DNA Transposable Elements; Diazonium Compounds; Genes, Bacterial; Genes, Essential; Halothiobacillus; Mutagenesis; Operon; Prokaryotic Cells; Sulfanilic Acids; Vibrio cholerae
PubMed: 31406332
DOI: 10.1038/s41564-019-0520-8 -
Molecules (Basel, Switzerland) Sep 2022As a promising therapy, photothermal therapy (PTT) converts near-infrared (NIR) light into heat through efficient photothermal agents (PTAs), causing a rapid increase in...
As a promising therapy, photothermal therapy (PTT) converts near-infrared (NIR) light into heat through efficient photothermal agents (PTAs), causing a rapid increase in local temperature. Considering the importance of PTAs in the clinical application of PTT, the safety of PTAs should be carefully evaluated before their widespread use. As a promising PTA, mesoporous polydopamine (MPDA) was studied for its clinical applications for tumor photothermal therapy and drug delivery. Given the important role that intestinal microflora plays in health, the impacts of MPDA on the intestine and on intestinal microflora were systematically evaluated in this study. Through biological and animal experiments, it was found that MPDA exhibited excellent biocompatibility, in vitro and in vivo. Moreover, 16S rRNA analysis demonstrated that there was no obvious difference in the composition and classification of intestinal microflora between different drug delivery groups and the control group. The results provided new evidence that MPDA was safe to use in large doses via different drug delivery means, and this lays the foundation for further clinical applications.
Topics: Animals; Diazonium Compounds; Gastrointestinal Microbiome; Hyperthermia, Induced; Indoles; Intestines; Nanoparticles; Phototherapy; Polymers; Pyridines; RNA, Ribosomal, 16S
PubMed: 36234997
DOI: 10.3390/molecules27196461 -
Chembiochem : a European Journal of... Aug 2023Aryl diazonium cations are versatile bioconjugation reagents due to their reactivity towards electron-rich aryl residues and secondary amines, but historically their...
Aryl diazonium cations are versatile bioconjugation reagents due to their reactivity towards electron-rich aryl residues and secondary amines, but historically their usage has been hampered by both their short lifespan in aqueous solution and the harsh conditions required to generate them in situ. Triazabutadienes address many of these issues as they are stable enough to endure multiple-step chemical syntheses and can persist for several hours in aqueous solution, yet upon UV-exposure rapidly release aryl diazonium cations under biologically-relevant conditions. This paper describes the synthesis of a novel maleimide-functionalized triazabutadiene suitable for site-selectively installing aryl diazonium cations into proteins at neutral pH; we show reaction with this molecule and a surface-cysteine of a thiol disulfide oxidoreductase. Through photoactivation of the site-selectively installed triazabutadiene motifs, we generate aryl diazonium functionality, which we further derivatize via azo-bond formation to electron-rich aryl species, showcasing the potential utility of this strategy for the generation of photoswitches or protein-drug conjugates.
Topics: Hydrogen-Ion Concentration; Membrane Proteins; Maleimides
PubMed: 37311168
DOI: 10.1002/cbic.202300313 -
Glycoconjugate Journal Oct 2015Carbohydrates, in addition to their metabolic functions, serve important roles as receptors, ligands, and structural molecules for diverse biological processes. Insight...
Carbohydrates, in addition to their metabolic functions, serve important roles as receptors, ligands, and structural molecules for diverse biological processes. Insight into carbohydrate biology and mechanisms has been aided by metabolic oligosaccharide engineering (MOE). In MOE, unnatural carbohydrate analogs with novel functional groups are incorporated into cellular glycoconjugates and used to probe biological systems. While MOE has expanded knowledge of carbohydrate biology, limited metabolism of unnatural carbohydrate analogs restricts its use. Here we assess metabolism of SiaDAz, a diazirine-modified analog of sialic acid, and its cell-permeable precursor, Ac4ManNDAz. We show that the efficiency of Ac4ManNDAz and SiaDAz metabolism depends on cell type. Our results indicate that different cell lines can have different metabolic roadblocks in the synthesis of cell surface SiaDAz. These findings point to roles for promiscuous intracellular esterases, kinases, and phosphatases during unnatural sugar metabolism and provide guidance for ways to improve MOE.
Topics: Carbohydrate Metabolism; Carbohydrates; Cell Line; Diazomethane; Esterases; Flow Cytometry; Glycoconjugates; Hexosamines; Humans; Metabolic Engineering; N-Acetylneuraminic Acid; Oligosaccharides
PubMed: 25957566
DOI: 10.1007/s10719-015-9593-7 -
ACS Chemical Biology Nov 2022Finding the targets of natural products is of key importance in both chemical biology and drug discovery, and deconvolution of cofactor interactomes contributes to the...
Finding the targets of natural products is of key importance in both chemical biology and drug discovery, and deconvolution of cofactor interactomes contributes to the functional annotation of the proteome. Identifying the proteins that underlie natural compound activity in phenotypic screens helps to validate the respective targets and, potentially, expand the druggable proteome. Here, we present a generally applicable protocol for the photoactivated immobilization of unmodified and microgram quantities of natural products on diazirine-decorated beads and their use for systematic affinity-based proteome profiling. We show that among 31 molecules of very diverse reported activity and biosynthetic origin, 25 could indeed be immobilized. Dose-response competition binding experiments using lysates of human or bacterial cells followed by quantitative mass spectrometry recapitulated targets of 9 molecules with <100 μM affinity. Among them, immobilization of coenzyme A produced a tool to interrogate proteins containing a HotDog domain. Surprisingly, immobilization of the cofactor flavin adenine dinucleotide (FAD) led to the identification of nanomolar interactions with dozens of RNA-binding proteins.
Topics: Humans; Proteome; Diazomethane; Biological Products; Flavin-Adenine Dinucleotide; Mass Spectrometry
PubMed: 36302507
DOI: 10.1021/acschembio.2c00500 -
International Journal of Molecular... Feb 2020The identification of molecules whose biological activity can be properly modulated by light is a promising therapeutic approach aimed to improve drug selectivity and...
The identification of molecules whose biological activity can be properly modulated by light is a promising therapeutic approach aimed to improve drug selectivity and efficacy on the molecular target and to limit the side effects compared to traditional drugs. Recently, two photo-switchable diastereomeric benzodiazopyrrole derivatives and have been reported as microtubules targeting agents (MTAs) on human colorectal carcinoma p53 null cell line (HCT 116 p53-/-). Their IC was enhanced upon Light Emitting Diode (LED) irradiation at 435 nm and was related to their form. Here we have investigated the photo-responsive behavior of the acid derivatives of and , namely, and , in phosphate buffer solutions at different pH. The comparison of the UV spectra, acquired before and after LED irradiation, indicated that the conversion of and is affected by the degree of ionization. The apparent rate constants were calculated from the kinetic data by means of fast UV spectroscopy and the conformers of the putative ionic species present in solution (pH range: 5.7-8.0) were modelled. Taken together, our experimental and theoretical results suggest that the photo-conversions of / into the corresponding forms and the thermal decay of / are dependent on the presence of diazonium form of /. Finally, a photo-reaction was detected only for after prolonged LED irradiation in acidic medium, and the resulting product was characterized by means of Liquid Chromatography coupled to High resolution Mass Spectrometry (LC-HRMS) and Nuclear Magnetic Resonance (NMR) spectroscopy.
Topics: Cell Proliferation; Chromatography, Liquid; Colorectal Neoplasms; Diazonium Compounds; HCT116 Cells; Humans; Magnetic Resonance Spectroscopy; Mass Spectrometry; Photochemotherapy; Pyrroles
PubMed: 32069905
DOI: 10.3390/ijms21041246 -
Molecules (Basel, Switzerland) Jul 2019The intramolecular C-H insertions of carbenes derived from 2-diazo-2-sulfamoylacetamides were studied. 2-Diazo-2-sulfamoylacetamides were first prepared from...
The intramolecular C-H insertions of carbenes derived from 2-diazo-2-sulfamoylacetamides were studied. 2-Diazo-2-sulfamoylacetamides were first prepared from chloroacetyl chloride and secondary amines through acylation followed by sequential treatments with sodium sulfite, phosphorus oxychloride, secondary amines, and 4-nitrobenzenesulfonyl azide. The results indicate that: (1) 2-diazo--dimethyl-2-(-diphenylsulfamoyl)acetamide can take the formal aromatic 1,5-C-H insertion in its -phenylsulfonamide moiety to afford the corresponding 1,3-dihydrobenzo[]isothiazole-3-carboxamide 2,2-dioxide derivative; (2) no aliphatic C-H insertions occur for 2-diazo-2-(-dialkylsulfamoyl)acetamides; and (3) for 2-diazo--phenyl-2-(-phenylsulfamoyl)acetamides, the formal aromatic 1,5-C-H insertion in the -phenylacetamide moiety is favorable to afford the corresponding 3-sulfamoylindolin-2-one derivatives as sole or major products. The intramolecular competitive aromatic 1,5-C-H insertion reactions of 2-diazo-2-sulfamoylacetamides with aryl groups on both amide and sulfonamide groups reveal that the -aryl substituents on acetamide are more active than those on sulfonamide. The chemoselectivity is controlled by electronic effect of the aryl group.
Topics: Acetamides; Carbon; Catalysis; Diazonium Compounds; Hydrogen; Methane; Sulfonamides
PubMed: 31330952
DOI: 10.3390/molecules24142628