A5101769478- Nitric Oxide and Endothelin Effects
- Hemoglobin structure and function
- Sulfur Compounds in Biology
- Electron Spin Resonance Studies
- Hemoglobinopathies and Related Disorders
- Oxidative Organic Chemistry Reactions
- Neuroscience of respiration and sleep
- Redox biology and oxidative stress
- Synthesis and Catalytic Reactions
- Eicosanoids and Hypertension Pharmacology
- Chemical Synthesis and Reactions
- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Peroxisome Proliferator-Activated Receptors
- Renin-Angiotensin System Studies
- Synthesis and Biological Evaluation
- Molecular Sensors and Ion Detection
- Neonatal Health and Biochemistry
- Chemical Reaction Mechanisms
- Genomics, phytochemicals, and oxidative stress
- Synthetic Organic Chemistry Methods
- Carbohydrate Chemistry and Synthesis
- Neurological Disease Mechanisms and Treatments
- Iron Metabolism and Disorders
- Inflammatory mediators and NSAID effects
Wake Forest University
2014-2023
National Cancer Institute
2012
Harbin Medical University
2012
Johns Hopkins University
2012
University of Baltimore
2012
University of Perugia
2012
University of Alabama
2006
Hadassah Academic College
2006
King's College Hospital
2006
Elizabeth City State University
2005
Experimental evidence suggests that nitric oxide (NO) and hydrogen sulfide (H2S) signaling pathways are intimately intertwined, with mutual attenuation or potentiation of biological responses in the cardiovascular system elsewhere. The chemical basis this interaction is elusive. Moreover, polysulfides recently emerged as potential mediators H2S/sulfide signaling, but their biosynthesis relationship to NO remain enigmatic. We sought characterize nature, biology, bioactivity key reaction...
Small increases in physiological nitrite concentrations have now been shown to mediate a number of biological responses, including hypoxic vasodilation, cytoprotection after ischemia/reperfusion, and regulation gene protein expression. Thus, while was until recently believed be biologically inert, it is recognized as potentially important signaling molecule therapeutic agent. Nitrite mediates through its reduction nitric oxide, via reactions with several heme-containing proteins. In this...
Cysteine sulfenic acid formation in proteins results from the oxidative modification of susceptible cysteine residues by hydrogen peroxide, alkyl hydroperoxides, and peroxynitrite. This species represents a biologically significant occurring during oxidant signaling or stress, it can modulate protein function. Most methods to identify such oxidatively modified rely on monitoring loss one more thiol group(s) selective labeling nascent groups following reduction oxidized proteins. Our previous...
Isoform-specific signaling of Akt, a major hub and prominent therapeutic target, remained poorly defined until recently. Subcellular distribution, tissue-specific expression, substrate specificity, posttranslational modifications are believed to underlie isoform-specific Akt. The studies reported here show inhibition Akt2 activity under physiologically relevant conditions oxidation created by PDGF-induced reactive oxygen species. Combined MS functional assays identified Cys124 located in the...
Recent studies distinguish the biological and pharmacological effects of nitroxyl (HNO) from its oxidized/deprotonated product nitric oxide (·NO), but lack HNO detection methods limits understanding in vivo mechanisms identification endogenous sources. We previously demonstrated that reaction with triarylphosphines provides aza-ylides HNO-derived amides, which may serve as stable biomarkers. now report a kinetic analysis for trapping by phosphines, ligations enzyme-generated HNO,...
Protein sulfenic acids are formed by the reaction of biologically relevant reactive oxygen species with protein thiols. Sulfenic acid formation modulates function enzymes and transcription factors either directly or through subsequent disulfide bonds. Identifying site, timing, conditions remains crucial to understanding cellular redox regulation. Current methods for trapping analyzing involve use dimedone other nucleophilic 1,3-dicarbonyl probes that form covalent adducts cysteine-derived...
Cellular exposure to reactive oxygen species induces rapid oxidation of DNA, proteins, lipids and other biomolecules. At the proteome level, cysteine thiol is a prominent post-translational process that implicated in normal physiology numerous pathologies. Methods for investigating protein include direct labeling with selective chemical probes indirect tag-switch techniques. Common both approaches blocking free thiols using electrophiles prevent post-lysis or thiol-mediated cross-reactions....
Cysteine sulfenic acids in proteins can be identified by their ability to form adducts with dimedone, but this reagent imparts no spectral or affinity tag for subsequent analyses of such tagged proteins. Given its similar reactivity toward cysteine acids, 1,3-cyclohexadione was synthetically modified an alcohol derivative and linked fluorophores based on isatoic acid 7-methoxycoumarin. The resulting compounds retain full specificity proteins, allowing incorporation the fluorescent label into...
Nitroxyl (HNO/NO-), the reduced form of nitric oxide, has gained attention based on its separate chemistry and biology from oxide. The inherent reactivity HNO requires new mechanistically unique donors for detailed study biology. Oxidation cyclohexanone oxime with lead tetraacetate yields 1-nitrosocyclohexyl acetate, whereas oxidation oximes in presence excess carboxylic acid gives various acyloxy nitroso compounds. These bright blue compounds exist as monomers indicated by their infrared,...
Nitroxyl (HNO) demonstrates a unique chemical and biological profile compared to nitric oxide (NO). Phosphorus NMR studies reveal that HNO reacts with triarylphosphines give the corresponding phosphine aza-ylide. In presence of properly situated electrophilic ester, aza-ylide undergoes Staudinger ligation yield an amide nitrogen atom being derived from HNO. These results define new reactivity provide basis detection methods.
Abstract Reactive oxygen intermediates (ROI) generated in response to receptor stimulation play an important role mediating cellular responses. We have examined the importance of reversible cysteine sulfenic acid formation naive CD8+ T cell activation and proliferation. observed that, within minutes activation, cells increased ROI levels a manner dependent upon Ag concentration. Increased resulted elevated total proteome. Analysis specific proteins revealed that protein tyrosine phosphatases...
Rationale: In the myocardium, redox/cysteine modification of proteins regulating Ca 2+ cycling can affect contraction and may have therapeutic value. Nitroxyl (HNO), one-electron-reduced form nitric oxide, enhances cardiac function in a manner that suggests reversible cysteine modifications contractile machinery. Objective: To determine effects HNO myofilament proteins. Methods Results: The HNO-donor, 1-nitrosocyclohexyl acetate, was found to act directly on proteins, increasing maximum...
It has been previously proposed that nitric oxide (NO) is the only biologically relevant nitrogen capable of activating enzyme soluble guanylate cyclase (sGC). However, recent reports implicate HNO as another possible activator sGC. Herein, we examine affect donors on activity purified bovine lung sGC and find that, indeed, this enzyme. Like NO, activation appears to occur via interaction with regulatory ferrous heme Somewhat unexpectedly, does not activate ferric form Finally, HNO-mediated...
Hydroxyurea represents an approved treatment for sickle cell anemia and a number of cancers. Chemiluminescence electron paramagnetic resonance spectroscopic studies show horseradish peroxidase catalyzes the formation nitric oxide from hydroxyurea in presence hydrogen peroxide. Gas chromatographic headspace analysis infrared spectroscopy also reveal production nitrous this reaction, which provides evidence nitroxyl, one-electron reduced form oxide. These reactions generate carbon dioxide,...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNew Ligands and Improved Enantioselectivities for the Asymmetric Dihydroxylation of OlefinsHeinrich Becker, S. Bruce King, Masahiko Taniguchi, Koenraad P. M. Vanhessche, K. Barry SharplessCite this: J. Org. Chem. 1995, 60, 13, 3940–3941Publication Date (Print):June 1, 1995Publication History Published online1 May 2002Published inissue 1 June 1995https://pubs.acs.org/doi/10.1021/jo00118a005https://doi.org/10.1021/jo00118a005research-articleACS...
The carboxylic acid group of the anti-inflammatory (AI) drugs indo-methacin, (S)-naproxen and ibuprofen was covalently linked via a two-carbon ethyl spacer to sulfohydroxamic moiety (CH2CH2SO2NHOH) furnish hybrid ester prodrugs that release nitric oxide (NO) nitroxyl (HNO). Biological data acquired for this hitherto unknown class ethanesulfohydroxamic showed (i) all compounds exhibited superior NO, but similar HNO, properties relative arylsulfohydroxamic acids, (ii) prodrug esters are more...