A5003201156- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Receptor Mechanisms and Signaling
- Radiopharmaceutical Chemistry and Applications
- Neuroscience and Neuropharmacology Research
- Pharmacological Receptor Mechanisms and Effects
- Neuropeptides and Animal Physiology
- Chemical Synthesis and Analysis
- Lanthanide and Transition Metal Complexes
- Fluorine in Organic Chemistry
- Medical Imaging Techniques and Applications
- Radioactive element chemistry and processing
- Neurotransmitter Receptor Influence on Behavior
- Cannabis and Cannabinoid Research
- Inorganic Chemistry and Materials
- Asymmetric Synthesis and Catalysis
- Oxidative Organic Chemistry Reactions
- Nitric Oxide and Endothelin Effects
- Chemical Reactions and Isotopes
- Molecular Junctions and Nanostructures
- Tuberculosis Research and Epidemiology
- Conducting polymers and applications
- Organic Electronics and Photovoltaics
- Toxoplasma gondii Research Studies
- Mass Spectrometry Techniques and Applications
National Institute of Allergy and Infectious Diseases
2021-2024
National Institutes of Health
2012-2023
Center for Information Technology
2011-2021
National Institute on Alcohol Abuse and Alcoholism
2008-2015
United States Naval Research Laboratory
1990-2015
National Institute on Drug Abuse
2007-2008
Catholic University of Korea
2008
National Institute of Mental Health
2008
National Heart Lung and Blood Institute
2008
University of New England
2007
The electronic structures of polyparaphenylene (PPP), polyacetylene (PA), and their derivatives with small energy gaps have been studied by the Hückel MNDO crystal orbital methods. effect nuclear relaxation heteroatomic substitution on (Eg) taken into account compelete geometry optimization using periodic boundary conditions as opposed to earlier cluster based calculations. Calculations were done following derivatives: polypyrrole (PPy), polythiophene (PT), polyisothianaphthene (PITN), poly...
A microreactor was applied to produce ortho-substituted [18F]fluoroarenes from the reactions of cyclotron-produced [18F]fluoride ion (t1/2 = 109.7 min) with diaryliodonium salts. The provided a very convenient means for running sequential rapidly small amounts reagents under well-controlled conditions, thereby allowing reaction kinetics be followed and Arrhenius activation energies (Ea) measured. Prepared symmetrical iodonium chlorides (Ar2I+Cl−) (<4 gave moderate (Ar 2-MeOC6H4, 51%) high Ph...
Crystallography, quantum chemistry and potentiometry of Zr( iv ) hydroxamate complexes: a combination tools to improve the development 89 Zr chelation for nuclear imaging.
Tuberculosis continues to be a global health threat, making bicyclic nitroimidazoles an important new class of therapeutics. A deazaflavin-dependent nitroreductase (Ddn) from Mycobacterium tuberculosis catalyzes the reduction such as PA-824, resulting in intracellular release lethal reactive nitrogen species. The N-terminal 30 residues Ddn are functionally but flexible or access multiple conformations, preventing structural characterization full-length, enzymatically active enzyme. Several...
The bicyclic 4-nitroimidazoles PA-824 and OPC-67683 represent a promising novel class of therapeutics for tuberculosis are currently in phase II clinical development. Both compounds pro-drugs that reductively activated by deazaflavin (F(420)) dependent nitroreductase (Ddn). Herein we describe the biochemical properties Ddn including optimal enzymatic turnover conditions substrate specificity. preference enzyme (S) isomer over (R) is directed presence long hydrophobic tail....
Seven-transmembrane receptors signal via G-protein- and β-arrestin-dependent pathways. We describe a peripheral CB1R antagonist (MRI-1891) highly biased toward inhibiting CB1R-induced β-arrestin-2 (βArr2) recruitment over G-protein activation. In obese wild-type βArr2-knockout (KO) mice, MRI-1891 treatment reduces food intake body weight without eliciting anxiety even at high dose causing partial brain occupancy. By contrast, the unbiased global rimonabant elicits in both strains, indicating...
Abstract Metals of interest for biomedical applications often need to be complexed and associated in a stable manner with targeting agent before use. Whereas the fundamentals most transition‐metal complexation processes have been thoroughly studied, Zr IV has somewhat neglected. This metal received growing attention recent years, especially nuclear medicine, use 89 Zr, which β + ‐emitter near ideal characteristics cancer imaging. However, best chelating known this radionuclide is...
Abstract Aryliodonium salts have become precursors of choice for the synthesis 18 F‐labeled tracers nuclear imaging. However, little is known on reactivity these compounds with heavy halides, that is, radioiodide and astatide, at radiotracer scale. In first comparative study radiohalogenation aryliodonium 125 I − 211 At , initial experiments a model compound highlight higher astatide compared to iodide, which could not be anticipated from trends previously observed within halogen series....
RP-HPLC and NMR studies showed that early lanthanides of <italic>SSSS-SSSS</italic>-M4DOTMA unprecedentedly favor the SAP conformation, while late adopt TSAP.
The (S)-2-nitro-6-(4-(trifluoromethoxy)benzyloxy)-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine named PA-824 (1) has demonstrated antitubercular activity in vitro and animal models is currently clinical trials. We synthesized derivatives at three positions of the 4-(trifluoromethoxy)benzylamino tail, these were tested for whole-cell against both replicating nonreplicating Mycobacterium tuberculosis (Mtb). In addition, we determined their kinetic parameters as substrates deazaflavin-dependent...
Proton transfer in bacteriorhodopsin from the cytoplasm to extracellular side is initiated protonated asp96 cytoplasmic region toward deprotonated Schiff base. This occurs transition photocycle late M state N state. To investigate this proton-transfer process, a quantum mechanics/molecular mechanics (QM/MM) model constructed E204Q mutant crystal structure. Three residues, asp96, asp85, and thr89, as well most of retinal chromophore base link lys216 are treated mechanically connected...
Both of the enantiomers 5-(3-hydroxyphenyl)-N-phenylethylmorphan with C9α-methyl, C9-methylene, C9-keto, and C9α- C9β-hydroxy substituents were synthesized pharmacologically evaluated. Three 10 compounds, (1R,5R,9S)-(−)-9-hydroxy-5-(3-hydroxyphenyl-2-phenylethyl-2-azabicyclo[3.3.1]nonane ((1R,5R,9S)-(−)-10), (1R,5S)-(+)-5-(3-hydroxyphenyl)-9-methylene-2-phenethyl-2-azabicyclo[3.3.1]nonane ((1R,5S)-(+)-14), (1R,5S,9R)-(−)-5-(3-hydroxyphenyl)-9-methyl-2-phenethyl-2-azabicyclo[3.3.1]nonane...
Treatment of (diacetoxyiodo)arenes (1a-1u) with cyclotron-produced [(18)F]fluoride ion rapidly affords no-carrier-added [(18)F]fluoroarenes (2a-2u) in useful yields and constitutes a new method for converting substituted iodoarenes into just two steps.
Abstract Infection with the apicomplexan protozoan Toxoplasma gondii can be life-threatening in immunocompromised hosts. Transmission frequently occurs through oral ingestion of T. bradyzoite cysts, which transition to tachyzoites, disseminate, and then form cysts containing bradyzoites central nervous system, resulting latent infection. Encapsulation by a cyst wall is critical for immune evasion, survival, transmission. O-glycosylation protein CST1 mucin-type O-glycosyltransferase (Txg )...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTImportance of energetics in the design small bandgap conducting polymersYong Sok Lee, Miklos Kertesz, and Ronald L. ElsenbaumerCite this: Chem. Mater. 1990, 2, 5, 526–530Publication Date (Print):September 1, 1990Publication History Published online1 May 2002Published inissue 1 September 1990https://pubs.acs.org/doi/10.1021/cm00011a012https://doi.org/10.1021/cm00011a012research-articleACS PublicationsRequest reuse permissionsArticle...
In the present report, we describe synthesis and structure–activity relationships of novel "four-arm" dihydropyrazoline compounds designed as peripherally restricted antagonists cannabinoid-1 receptor (CB1R). A series racemic 3,4-diarylpyrazolines were synthesized evaluated initially in CB1 binding assays. The compounds, to limit brain penetrance decreased lipophilicity, showed high affinity for CB1R potent vitro antagonist activities. Promising with activity tissue distribution studies....
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBand structure calculation of extended poly(copper phthalocyanine) one-dimensional and two-dimensional polymersPedro Gomez-Romero, Yong Sok Lee, Miklos KerteszCite this: Inorg. Chem. 1988, 27, 20, 3672–3675Publication Date (Print):October 1, 1988Publication History Published online1 May 2002Published inissue 1 October 1988https://pubs.acs.org/doi/10.1021/ic00293a049https://doi.org/10.1021/ic00293a049research-articleACS PublicationsRequest reuse...
Molecular dynamics simulations on quantum energy surfaces are carried out to study the effects of perturbing electric fields proton transport (PT) in protonated water chains. As an idealized model a hydrophobic cavity interior protein molecules confined into carbon nanotube (CNT). The chain connects hydrated hydronium ion (H3O+) at one end CNT and imidazole molecule other end. Without PT from donor acceptor occurs picosecond time scale. External perturbations created by varying intensities,...
Abstract Diaryliodonium salts allow the efficient incorporation of cyclotron‐produced [ 18 F]fluoride ions into electron‐rich and electron‐deficient arenes to provide potential radiotracers for molecular imaging in vivo with positron emission tomography (PET). This process (ArI + Ar′+ F − →Ar F+Ar′I) is still not well understood mechanistically. To better understand this similar reactions, it would be valuable structures diaryliodonium organic media, where reactions are typically conducted....
Conformational restraint in the N-substituent of enantiomeric 5-(3-hydroxyphenyl)morphans was conferred by addition a cyclopropane ring or double bond. All possible enantiomers and isomers N-substituted compounds were synthesized. Opioid receptor binding assays indicated that some them had about 20-fold higher μ-affinity than compound with an N-phenylpropyl substituent (Ki = 2−450 nM for examined various N-substituents). Most acted unusually as inverse agonists [35S]GTP-γ-S functional assay...
Eighteen kilodalton translocator protein (TSPO) is an important target for drug discovery and clinical molecular imaging of brain peripheral inflammatory processes. PK 11195 [1a; 1-(2-chlorophenyl)-N-methyl-(1-methylpropyl)-3-isoquinoline carboxamide] the major prototypical high-affinity ligand TSPO. Elucidation solution structure 1a interest understanding small-molecule interactions with lipophilic binding site Dynamic (1)H/(13)C NMR spectroscopy revealed four quite stable but...
We have designed orally bioavailable, non-brain-penetrant antagonists of the cannabinoid-1 receptor (CB1R) with a built-in biguanide sensor to mimic 5′-adenosine monophosphate kinase (AMPK) activation for treating obesity-associated co-morbidities. A series 3,4-diarylpyrazolines bearing rational pharmacophoric pendants limit brain penetration were synthesized and evaluated in CB1R ligand binding assays recombinant AMPK assays. The compounds displayed high affinity potent antagonist...