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Molecules (Basel, Switzerland) Jan 2022A family of oxazaborines, diazaborinones, triazaborines, and triazaborinones was prepared by reaction of polarized ethylenes, such as β-enaminoamides, with...
A family of oxazaborines, diazaborinones, triazaborines, and triazaborinones was prepared by reaction of polarized ethylenes, such as β-enaminoamides, with 4-methylbenzenediazonium tetraphenylborates. The reaction conditions (stirring in CHCl at room temperature (Method A) or stirring with CHCOONa in CHCl at room temperature (Method B) or refluxing in the CHCl/toluene mixture (Method C)) controlled the formation and relative content of these compounds in the reaction mixtures from one to three products. Substituted oxazaborines gradually rearranged into diazaborinones at 250 °C. The prepared compounds were characterized by H NMR, C NMR, IR, and UV-Vis spectroscopy, HRMS, or microanalysis. The structure of individual compounds was confirmed by B NMR, N NMR, 1D NOESY, and X-ray analysis. The mechanism of reaction of enaminoamides with 4-methylbenzenediazonium tetraphenylborate was proposed.
PubMed: 35056681
DOI: 10.3390/molecules27020367 -
Chembiochem : a European Journal of... Apr 2020Studying protein-protein interactions (PPIs) is useful for understanding cellular functions and mechanisms. Evaluating these PPIs under conditions as similar as possible... (Review)
Review
Studying protein-protein interactions (PPIs) is useful for understanding cellular functions and mechanisms. Evaluating these PPIs under conditions as similar as possible to native conditions can be achieved using photo-crosslinking methods because of their on-demand ability to generate reactive species in situ by irradiation with UV light. Various fusion tag, metabolic incorporation, and amber codon suppression approaches using various crosslinkers containing aryl azide, benzophenone, and diazirines have been applied in live cells. Mass spectrometry and immunological techniques are used to identify crosslinked proteins based on their capture transient and context-dependent interactions. Herein we discuss various incorporation methods and crosslinkers that have been used for interactome mapping in live cells.
Topics: Cholera Toxin; Cross-Linking Reagents; Diazomethane; Humans; Ligases; Lysine; Protein Processing, Post-Translational; Proteins; Ultraviolet Rays
PubMed: 31794116
DOI: 10.1002/cbic.201900600 -
Current Drug Metabolism 2015Cytochrome P450 (CYP450) enzymes are the most important metabolizing enzyme family exists among all organs. Apart from their role in the deactivation of most endogenous... (Review)
Review
Cytochrome P450 (CYP450) enzymes are the most important metabolizing enzyme family exists among all organs. Apart from their role in the deactivation of most endogenous compounds and xenobiotics, they also mediate most procarcinogens oxidation to ultimate carcinogens. There are several modes of CYP450s activation of procarcinogens. 1) Formation of epoxide and diol-epoxides intermediates, such as CYP1A1 and CYP1B1 mediates PAHs oxidation to epoxide intermediates; 2) Formation of diazonium ions, such as CYP2A6, CYP2A13 and CYP2E1 mediates activation of most nitrosamines to unstable metabolites, which can rearrange to give diazonium ions. 3) Formation of reactive semiquinones and quinines, such as CYP1A1 and CYP1B1 transformation of estradiol to catechol estrogens, subsequently formation semiquinones; 4) Formation of toxic O-esterification, such as CYP1A1 and CYP1A2 metabolizes PhIP to N(2)-acetoxy-PhIP and N(2)-sulfonyloxy-PhIP, which are carcinogenic metabolites. 5) Formation of free radical, such as CYP2E1 is involved in activation tetrachloromethane to free radicals. While for CYP2B6 and CYP2D6, only a minor role has been found in procarcinogens activation. In addition, as the gene polymorphisms reflected, the polymorphisms of CYP1A1 (-3801T/C and -4889A/G), CYP1A2 (- 163C/A and -2467T/delT), CYP1B1 (-48G/C, -119G/T and -432G/C), CYP2E1 (-1293G/C and -1053 C/T) have been associated with an increased risk of lung cancer. The polymorphisms CYP1A1 (-3801T/C and -4889A/G), and CYP2E1 (PstI/Rsa and 9-bp insertion) have an association with higher risk colon cancers, whereas CYP1A2 (-163C/A and -3860G/A) polymorphism is found to be among the protective factors. The polymorphisms CYP1A1 (-3801T/C and -4889A/G), CYP1B1 -432G/C, CYP2B6 (-516G/T and -785A/G) may increase the risk of breast cancer. In conclusion, CYP1A1, CYP1A2, CYP1B1, CYP2A6, and CYP2E1 are responsible for most of the procarcinogens activation, and their gene polymorphisms are associated with the risk of cancers.
Topics: Carcinogens; Cytochrome P-450 Enzyme System; Humans; Neoplasms; Oxidation-Reduction; Polymorphism, Genetic; Risk
PubMed: 26652254
DOI: 10.2174/138920021610151210164501 -
ACS Chemical Biology Feb 2021Protein poly-ADP-ribosylation (PARylation) is a heterogeneous and dynamic post-translational modification regulated by various writers, readers, and erasers. It...
Protein poly-ADP-ribosylation (PARylation) is a heterogeneous and dynamic post-translational modification regulated by various writers, readers, and erasers. It participates in a variety of biological events and is involved in many human diseases. Currently, tools and technologies have yet to be developed for unambiguously defining readers and erasers of individual PARylated proteins or cognate PARylated proteins for known readers and erasers. Here, we report the generation of a bifunctional nicotinamide adenine dinucleotide (NAD) characterized by diazirine-modified adenine and clickable ribose. By serving as an excellent substrate for poly-ADP-ribose polymerase 1 (PARP1)-catalyzed PARylation, the generated bifunctional NAD enables photo-cross-linking and enrichment of PARylation-dependent interacting proteins for proteomic identification. This bifunctional NAD provides an important tool for mapping cellular interaction networks centered on protein PARylation, which are essential for elucidating the roles of PARylation-based signals or activities in physiological and pathophysiological processes.
Topics: Azides; Click Chemistry; Cross-Linking Reagents; Diazomethane; HEK293 Cells; Humans; NAD; Poly (ADP-Ribose) Polymerase-1; Poly ADP Ribosylation; Protein Processing, Post-Translational; Proteome; Proteomics; Ultraviolet Rays
PubMed: 33524253
DOI: 10.1021/acschembio.0c00937 -
Chemical Society Reviews Aug 2016Interest in homogeneous gold catalysis has undergone a marked increase. As strong yet air- and moisture-tolerant π-acids, cationic gold(i) complexes have been shown to... (Review)
Review
Interest in homogeneous gold catalysis has undergone a marked increase. As strong yet air- and moisture-tolerant π-acids, cationic gold(i) complexes have been shown to catalyze diverse transformations of alkenes, alkynes and allenes, opening new opportunities for chemical synthesis. The development of efficient asymmetric variants is required in order to take full advantage of the preparative potential of these transformations. During the last few years, the chemical community has achieved tremendous success in the area. This review highlights the updated progress (2011-2015) in enantioselective gold catalysis. The discussion is classified according to the π-bonds activated by gold(i), in an order of alkynes, allenes and alkenes. Other gold activation modes, such as σ-Lewis acid catalyzed reactions and transformations of diazo compounds are also discussed.
Topics: Alkadienes; Alkenes; Alkynes; Catalysis; Cycloaddition Reaction; Diazonium Compounds; Gold; Lewis Acids; Oxygen
PubMed: 26890605
DOI: 10.1039/c5cs00929d -
Angewandte Chemie (International Ed. in... Nov 2023The development of Alzheimer's disease (AD) drugs has recently witnessed substantial achievement. To further enhance the pool of drug candidates, it is crucial to...
The development of Alzheimer's disease (AD) drugs has recently witnessed substantial achievement. To further enhance the pool of drug candidates, it is crucial to explore non-traditional therapeutic avenues. In this study, we present the use of a photolabile curcumin-diazirine analogue, CRANAD-147, to induce changes in properties, structures (sequences), and neurotoxicity of amyloid beta (Aβ) species both in cells and in vivo. This manipulation was achieved through irradiation with LED light or molecularly generated light, dubbed as "molecular light", emitted by the chemiluminescence probe ADLumin-4. Next, aided by molecular chemiluminescence imaging, we demonstrated that the combination of CRANAD-147/LED or CRANAD-147/ADLumin-4 (molecular light) could effectively slow down the accumulation of Aβs in transgenic 5xFAD mice in vivo. Leveraging the remarkable tissue penetration capacity of molecular light, phototherapy employing the synergistic effect of a photolabile Aβ ligand and molecular light emerges as a promising alternative to conventional AD treatment interventions.
Topics: Mice; Animals; Alzheimer Disease; Amyloid beta-Peptides; Curcumin; Diazomethane; Mice, Transgenic; Phototherapy; Disease Models, Animal
PubMed: 37721455
DOI: 10.1002/anie.202312519 -
Current Protocols in Protein Science Sep 2020Peripheral membrane proteins participate in numerous biological pathways. Thus, methods to analyze their membrane-binding characteristics have become important. In this...
Peripheral membrane proteins participate in numerous biological pathways. Thus, methods to analyze their membrane-binding characteristics have become important. In this report, we detail protocols for the synthesis and utilization of a photoactivable fluorescent lipid as a reporter to monitor membrane binding of proteins. The assay, referred to as proximity-based labeling of membrane-associated proteins (PLiMAP), is based on UV activation of a fluorescent lipid reporter, which in turn crosslinks with proteins bound to membranes and renders them fluorescent. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Synthesis of BODIPY-diazirine phosphatidylethanolamine (BDPE) Basic Protocol 2: Preparation of BDPE-containing liposomes Basic Protocol 3: Performing PLiMAP with a candidate protein Basic Protocol 4: Quantitation of liposome-binding properties of the candidate protein from analyzing in-gel fluorescence Support Protocol: Purification of GST-2×P4M domain of SidM protein.
Topics: Animals; Boron Compounds; Cell Membrane; Diazomethane; Fluorescent Dyes; Humans; Liposomes; Membrane Proteins; Phosphatidylethanolamines; Phosphatidylinositol Phosphates; Photochemical Processes; Protein Binding; Spectrometry, Fluorescence
PubMed: 32603530
DOI: 10.1002/cpps.110 -
Biomacromolecules May 2018Bioadhesives are a current unmet clinical need for mending of blood contacting soft tissues without inducing thrombosis. Recent development of carbene precursor...
Bioadhesives are a current unmet clinical need for mending of blood contacting soft tissues without inducing thrombosis. Recent development of carbene precursor bioadhesives with the advantages of on-demand curing, tuneable modulus, and wet adhesion have been synthesized by grafting diazirine onto poly (amidoamine) (PAMAM-G5) dendrimers. Herein, the structure activity relationships of platelet adhesion and activation is evaluated for the first time on the cured PAMAM-g-diazirine bioadhesives. Three strategies were employed to prevent healthy human donor platelets from adhering and activating on light-cured bioadhesive surfaces: (1) Attenuation of cationic surface charge, (2) antifouling composites by incorporating heparin and alginate in uncured formulation, and (3) heparin wash of cured bioadhesive surface. Topographical imaging of cured and ethanol dehydrated bioadhesive surfaces was used to quantify the adhered and activated platelets with scanning electron microscopy, whose resolution allowed identification of round senescent, short dendritic, and long dendritic platelets. Cured surfaces of PAMAM-g-diazirine (15%) had 10300 ± 500 adhered platelets mm with 99.7% activation into short/long dendritic cells. Reduction of primary amines by higher degree of diazirine grafting or capping of free amines by acetylation reduces platelet adherence (2400 ± 200 vs 3000 ± 300, respectively). Physical incorporation of heparin and alginate in the formulations reduced the activated platelet; 1300 ± 300 and 300 ± 50, activated platelets mm, in comparison with additive free adhesive formulation. Similarly, heparin rinse of the surface of additive free bioadhesive reduced the activated platelet to platelets of heparin composites at 600 ± 100 platelets mm. PAMAM-g-diazirine (15%) bioadhesive retained the photocured mechanical properties and lap shear adhesion despite the addition of heparin and alginate additives.
Topics: Adhesives; Blood Platelets; Cell Adhesion; Cross-Linking Reagents; Diazomethane; Fibrinolytic Agents; Humans; Hydrogels; Methane; Polyamines
PubMed: 29425441
DOI: 10.1021/acs.biomac.8b00074 -
Organic & Biomolecular Chemistry Sep 2019Aryl transfer reactions from arenediazonium salts have started to make their impact in chemical biology with initial forays in the arena of arylative modifications and... (Review)
Review
Aryl transfer reactions from arenediazonium salts have started to make their impact in chemical biology with initial forays in the arena of arylative modifications and bio-conjugations of amino acids, peptides and proteins. The unique multimodal reactivity of arenediazonium salts, ranging from thermal or photochemical radical chain reactions, Pd-catalyzed coupling to arylazo-coupling reactions, all under distinct but mild conditions, provides multiple options for side chain modifications of amino acids and peptides and in addition, site-selective protein conjugation and labelling, protein immobilization, azo-bridged macrocyclization, etc. under bio-ambient conditions. The purpose of this review is to highlight these recent advances and to stimulate interest towards broader applications of arenediazonium salts as aryl transfer agents in bioconjugation reactions.
Topics: Amino Acids; Diazonium Compounds; Hydrocarbons, Aromatic; Molecular Conformation; Salts
PubMed: 31469151
DOI: 10.1039/c9ob01471c -
Chemical Research in Toxicology Feb 2024A thorough literature review was undertaken to understand how the pathways of -nitrosamine transformation relate to mutagenic potential and carcinogenic potency in... (Review)
Review
A thorough literature review was undertaken to understand how the pathways of -nitrosamine transformation relate to mutagenic potential and carcinogenic potency in rodents. Empirical and computational evidence indicates that a common radical intermediate is created by CYP-mediated hydrogen abstraction at the α-carbon; it is responsible for both activation, leading to the formation of DNA-reactive diazonium species, and deactivation by denitrosation. There are competing sites of CYP metabolism (e.g., β-carbon), and other reactive species can form following initial bioactivation, although these alternative pathways tend to decrease rather than enhance carcinogenic potency. The activation pathway, oxidative dealkylation, is a common reaction in drug metabolism and evidence indicates that the carbonyl byproduct, e.g., formaldehyde, does not contribute to the toxic properties of -nitrosamines. Nitric oxide (NO), a side product of denitrosation, can similarly be discounted as an enhancer of -nitrosamine toxicity based on carcinogenicity data for substances that act as NO-donors. However, not all -nitrosamines are potent rodent carcinogens. In a significant number of cases, there is a potency overlap with non--nitrosamine carcinogens that are not in the Cohort of Concern (CoC; high-potency rodent carcinogens comprising aflatoxin-like-, -nitroso-, and alkyl-azoxy compounds), while other -nitrosamines are devoid of carcinogenic potential. In this context, mutagenicity is a useful surrogate for carcinogenicity, as proposed in the ICH M7 (R2) (2023) guidance. Thus, in the safety assessment and control of -nitrosamines in medicines, it is important to understand those complementary attributes of mechanisms of mutagenicity and structure-activity relationships that translate to elevated potency versus those which are associated with a reduction in, or absence of, carcinogenic potency.
Topics: Humans; Animals; Carcinogens; Nitrosamines; Mutagens; Rodentia; Carcinogenesis; Carbon; Mutagenicity Tests
PubMed: 38316048
DOI: 10.1021/acs.chemrestox.3c00327