A5018216495- Pesticide Exposure and Toxicity
- Cholinesterase and Neurodegenerative Diseases
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Peptidase Inhibition and Analysis
- Radiopharmaceutical Chemistry and Applications
- Insect and Pesticide Research
- Pneumocystis jirovecii pneumonia detection and treatment
- Metal complexes synthesis and properties
- Trace Elements in Health
- Computational Drug Discovery Methods
- Pesticide Residue Analysis and Safety
- Paraoxonase enzyme and polymorphisms
- Biosimilars and Bioanalytical Methods
- Muscle and Compartmental Disorders
- Neuropeptides and Animal Physiology
- RNA and protein synthesis mechanisms
- Pharmacological Effects and Assays
- Antimicrobial Resistance in Staphylococcus
- Pesticide and Herbicide Environmental Studies
- Analytical Chemistry and Chromatography
- Pharmacological Effects and Toxicity Studies
- Antimicrobial Peptides and Activities
- Forensic Toxicology and Drug Analysis
- Cancer therapeutics and mechanisms
United States Army
2015-2025
Walter Reed Army Institute of Research
2009-2020
United States Department of the Army
2012
University of Nebraska Medical Center
2009
Johns Hopkins University
2000-2006
University of Maryland, Baltimore
2006
University of North Carolina Wilmington
2003-2006
Northwestern University
2006
University of California, San Diego
2005
A new N2S(alkylthiolate)-coordinated Pb2+ compound {2-methyl-1-[methyl(2-pyridin-2-ylethyl)amino]propane-2-thiolatolead perchlorate, [PATH-Pb][ClO4]} has been synthesized and characterized by X-ray diffraction 207Pb NMR. [PATH-Pb]+ is the first reported three-coordinate Pb complex with an alkanethiolate ligand and, hence, a good model for Pb-cysteine interactions in proteins. The center displays distorted trigonal-planar geometry. Pb-S bond lengths are extremely short (2.590(10) 2.597(10)...
Abstract Purpose Exposure to chemical threat agents (CTAs), including nerve agents, the vesicating agent sulfur mustard, and opioids, remains a significant warfighter civilian populations. Definitive analytical methods verify exposure CTAs require shipping refrigerated or frozen biomedical samples reference laboratories for analysis. Logistical financial burdens arise as transport of is subject strict restrictions complex packaging, which, if done incorrectly, can lead sample deterioration....
The protein tristetraprolin (TTP, also known as NUP475 and TIS11) is a nonclassical zinc finger that involved in regulating the inflammatory response. Specifically, TTP binds to AU-rich sequence elements located at 3'-untranslated region of cytokine mRNAs forming complex degraded by exosome. nucleic acid binding comprised two CysX8CysX5CysX3His domains are activated presence zinc. A two-domain construct (TTP-2D) has been cloned overexpressed E. coli. TTP-2D picks up visible red coloration...
Recently we described a novel di-benzene-pyrylium-indolene (BAS00127538) inhibitor of Lipid II. BAS00127538 (1-Methyl-2,4-diphenyl-6-((1E,3E)-3-(1,3,3-trimethylindolin-2-ylidene)prop-1-en-1-yl)pyryl-1-ium) tetrafluoroborate is the first small molecule II and structurally distinct from natural agents that bind II, such as vancomycin. Here, describe synthesis biological evaluation 50 new analogs designed to explore structure-activity relationships scaffold. The results this study indicate an...
A novel zinc(II) hydroxide complex with a rare alkylthiolate donor in the coordination sphere is formed aqueous solution from dissolution of zinc alkyl precursor (PATH)ZnCH3 (PATH = 2-methyl-1-[methyl(2-pyridin-2-ylethyl)amino]propane-2-thiolate) H2O and protonolysis Zn−C bond to give (PATH)ZnOH (1). The has been shown promote hydrolysis 4-nitrophenyl acetate (4-NA) by detailed kinetic study first functional model for form enzyme peptide deformylase. From fit sigmoidal pH−rate profile pKa...
We evaluated the effects of conjugated enzyme-nerve agent product resulting from inhibition bioscavenger human serum butyrylcholinesterase (Hu BChE) by nerve agents soman or VX. Rats were trained on a multiple Fixed-Ratio 32, Extinction 30 sec. (FR32, Ext30) schedule food reinforcement and then injected (i.m.) with Hu BChE (30 mg/kg), equivalent amounts BChE-soman conjugate (GDC), BChE-VX conjugate, oxotremorine (OXO) (0.316 mg/kg) vehicle (n = 8, each group). On day injection 10 subsequent...
Human serum butyrylcholinesterase (Hu BChE) is a promising therapeutic against the toxicity of chemical warfare nerve agents. We have showed previously that recombinant (r) Hu BChE can be expressed at very high levels, 400 to 600 U/ml in mouse blood, by delivering gene using adenovirus (Ad). Here, we report biochemical properties Ad-expressed full-length and truncated rHu blood. The molecular sizes subunit its oligomers were similar those native BChE, although only small portion underwent...
A new tridentate N2Sthiolate ligand, PATH, has been prepared and includes a sterically hindered aliphatic thiolate donor as cysteine mimic. PATH was employed in the synthesis of monomeric complexes [(PATH)MIIBr] [(PATH)MIINCS] (M = Zn, Co), which have characterized by X-ray diffraction. These are close structural analogues His2Cys site found peptide deformylase.
The zinc(II) complex (PATH)ZnOH, where PATH is an N2S(thiolate) ligand, has been investigated for its ability to promote the hydrolysis of phosphate triester tris(4-nitrophenyl) (TNP). TNP was examined as a function PATH-zinc(II) concentration, substrate and pH in water/ethanol mixture (66:33 v/v) at 25 degrees C. reaction first order both substrate, second-order rate constants were derived from linear plots observed pseudo-first-order versus zinc concentration different values. A pH-rate...
The atypical butyrylcholinesterase (aBuChE) from Oryzias latipes shares approximately 65% sequence similarity to both acetylcholinesterase and was studied for its capacity spontaneously reactivate following inhibition by organophosphorus nerve agents. full-length aBuChE protein expressed purified cabbage loopers (Trichoplusia ni larvae) infected with an orally active form of baculovirus. Like other cholinesterases, inhibited all G- V-type Interestingly, able undergo spontaneous reactivation...
Theopioid epidemic is a rapidly growing crisis around the world. Current models forpharmacokinetic assessment of countermeasures use African green monkeys (AGM). Arapid, sensitive and selective method was developed validated usingLC‐MS/MS for determination naloxone 6α‐naloxol in AGM plasma. Samplepreparation involved simple solid phase extraction (SPE) using ahydrophilic‐lipophilic‐balanced reversed‐phase cartridge. Separation naloxoneand achieved on Halo C18, 2.1 × 50 mm, 2.7μ analytical...