A5039280742- Carbohydrate Chemistry and Synthesis
- Glycosylation and Glycoproteins Research
- Amino Acid Enzymes and Metabolism
- Enzyme Catalysis and Immobilization
- Enzyme Structure and Function
- Chemical Synthesis and Analysis
- Analytical Chemistry and Chromatography
- Force Microscopy Techniques and Applications
- Molecular Junctions and Nanostructures
- Nanofabrication and Lithography Techniques
- Antibiotic Resistance in Bacteria
- Monoclonal and Polyclonal Antibodies Research
- Protein Structure and Dynamics
- thermodynamics and calorimetric analyses
- Biochemical and Molecular Research
- Lipid Membrane Structure and Behavior
- Nitric Oxide and Endothelin Effects
- Protein Interaction Studies and Fluorescence Analysis
- Molecular spectroscopy and chirality
- Photosynthetic Processes and Mechanisms
- Antimicrobial Peptides and Activities
- Drug Transport and Resistance Mechanisms
- Metabolism and Genetic Disorders
- Microbial Metabolic Engineering and Bioproduction
- Escherichia coli research studies
Duke University
2011-2025
Duke Medical Center
2001-2017
Duke University Hospital
2001-2017
Changzhou University
2011
University of California, Los Angeles
2000-2005
Sahlgrenska University Hospital
2005
Howard Hughes Medical Institute
2000-2003
University of Michigan
2001
University of St Andrews
1999
Simon Fraser University
1997
The inhibition of protein−carbohydrate interaction provides a powerful therapeutic strategy for the treatment myriad human diseases. To date, application such approaches have been frustrated by inherent low affinity carbohydrate ligands their protein receptors. Because lectins typically exist in multimeric assemblies, variety polyvalent saccharide prepared search high affinity. cluster glycoside effect, or observation derived from multivalency oligosaccharide ligands, apparently represents...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA Direct Measure of the Contribution Solvent Reorganization to Enthalpy BindingMary C. Chervenak and Eric J. TooneCite this: Am. Chem. Soc. 1994, 116, 23, 10533–10539Publication Date (Print):November 1, 1994Publication History Published online1 May 2002Published inissue 1 November 1994https://pubs.acs.org/doi/10.1021/ja00102a021https://doi.org/10.1021/ja00102a021research-articleACS PublicationsRequest reuse permissionsArticle...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnzymes in organic synthesis. 47. Active-site model for interpreting and predicting the specificity of pig liver esteraseEric J. Toone, Michael Werth, Bryan JonesCite this: Am. Chem. Soc. 1990, 112, 12, 4946–4952Publication Date (Print):June 1, 1990Publication History Published online1 May 2002Published inissue 1 June 1990https://pubs.acs.org/doi/10.1021/ja00168a047https://doi.org/10.1021/ja00168a047research-articleACS PublicationsRequest reuse...
Many key regulatory proteins, including members of the Ras family GTPases, are modified at their C terminus by a process termed prenylation. This processing is initiated addition an isoprenoid lipid, and proteins further proteolytic event methylation C-terminal prenylcysteine. Although biological consequences prenylation have been characterized extensively, contributions prenylcysteine to functions not well understood. reaction catalyzed enzyme isoprenylcysteine carboxyl methyltransferase...
The challenge in the synthesis of protein-polymer conjugates for biological applications is to synthesize a stoichiometric (typically 1:1) conjugate protein with monodisperse polymer, good retention activity, significantly improved pharmacokinetics and increased bioavailability, hence vivo efficacy. Here we demonstrate, using myoglobin as an example, general route grow PEG-like poly(oligo(ethylene glycol) methyl ether methacrylate) [poly(OEGMA)], low polydispersity high yield, solely from...
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTS−N Dissociation Energies of S-Nitrosothiols: On the Origins Nitrosothiol Decomposition RatesMichael D. Bartberger, Joseph Mannion, Steven C. Powell, Jonathan S. Stamler, K. N. Houk, and Eric J. TooneView Author Information Department Chemistry Biochemistry University California, Los Angeles, California 90095 Chemistry, Duke Durham, North Carolina 27708 Howard Hughes Medical Institute Departments Medicine Center, Cite this: Am. Chem. Soc....
The UDP-3- O -( R -3-hydroxyacyl)- N -acetylglucosamine deacetylase LpxC is an essential enzyme in the biosynthesis of lipid A, outer membrane anchor lipopolysaccharide and lipooligosaccharide Gram-negative bacteria. development LpxC-targeting antibiotics toward clinical therapeutics has been hindered by limited antibiotic profile reported non-hydroxamate inhibitors unexpected cardiovascular toxicity observed certain hydroxamate non–hydroxamate-based inhibitors. Here, we report preclinical...
To investigate the molecular basis of antigenic mimicry by peptides, we studied a panel closely related mAbs directed against cell-wall polysaccharide group A Streptococcus . These antibodies have restricted V -gene usage, indicating shared mechanism binding to single epitope. Epitope mapping studies using synthetic fragments supported this conclusion. All isolated crossreactive peptides from phage-displayed libraries, and competition indicated that many bind at or near carbohydrate site....
ADVERTISEMENT RETURN TO ISSUEPREVArticleCalorimetric Analysis of the Binding Lectins with Overlapping Carbohydrate-Binding Ligand SpecificitiesMary C. Chervenak and Eric J. TooneCite this: Biochemistry 1995, 34, 16, 5685–5695Publication Date (Print):April 25, 1995Publication History Published online1 May 2002Published inissue 25 April 1995https://pubs.acs.org/doi/10.1021/bi00016a045https://doi.org/10.1021/bi00016a045research-articleACS PublicationsRequest reuse permissionsArticle...
A study of the binding Shiga-like toxin 1 (SLT-1) to P(k) trisaccharide [methyl 4-O-(4-O-alpha-D-galactopyranosyl)-4-O-beta-D- glucopyranoside] and its constituent dissacharides was carried out. The represents carbohydrate recognition domain neutral glycolipid receptor SLT-1, globotriosylceramide (GbOse3). constant for soluble pentameric B-subunit is weak, with a K(a) (0.5-1) x 10(3) M-1 monomer. Scatchard analysis data indicates five identical non-interacting sites per pentamer no...
The binding of the mannose/glucose specific lectins from Canavalia ensiformis (concanavalin A) and Dioclea grandiflora to a series C-glucosides mannosides was studied by titration microcalorimetry fluorescence anisotropy titration. These closely related share specificity for trimannoside methyl 3,6-di-O-(α-d-mannopyranosyl)-α-d-mannopyranoside, are useful model system addressing feasibility differentiating between with overlapping carbohydrate specificities. ligands were designed address two...
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTTheory, Spectroscopy, and Crystallographic Analysis of S-Nitrosothiols: Conformational Distribution Dictates Spectroscopic BehaviorMichael D. Bartberger, K. N. Houk, Steven C. Powell, Joseph Mannion, Kenneth Y. Lo, Jonathan S. Stamler, Eric J. TooneView Author Information Department Chemistry Biochemistry University California Los Angeles, 90095-1569 Chemistry, Duke Durham, North Carolina 27708 The Howard Hughes Medical Institute Departments...
To better understand the origin of multivalency effects in ligand binding, binding a series mono-, bi-, tri- and tetravalent carboxylate ligands to Ca(II) was examined by isothermal titration calorimetry (ITC). The data are inconsistent with an entropic enhanced affinity, but rather show that at least this instance effect is enthalpic origin. Analysis using Jencks model shows addition incremental "ligands" produces unfavorable interaction entropy more than offset strongly favorable enthalpy....
ABSTRACT Antibiotic therapy is the most commonly used strategy to control pathogenic infections; however, it has contributed generation of antibiotic-resistant bacteria. To circumvent this emerging problem, we are searching for compounds that target bacterial virulence factors rather than their viability. Pseudomonas aeruginosa , an opportunistic human pathogen, possesses a type III secretion system (T3SS) as one major by which secretes and translocates T3 effector proteins into host cells....
Using a screen for Wnt/β-catenin inhibitors, family of 8-hydroxyquinolone derivatives with in vivo anti-cancer properties was identified. Analysis microarray data the lead compound N-((8-hydroxy-7-quinolinyl) (4-methylphenyl)methyl)benzamide (HQBA) using Connectivity Map database suggested that it is an iron chelator mimics hypoxic response. HQBA chelates Fe2+ dissociation constant ∼10−19 M, much weaker binding to Fe3+ and other transition metals. inhibited proliferation multiple cell lines...
Abstract Conformational dynamics plays an important role in enzyme catalysis, allosteric regulation of protein functions and assembly macromolecular complexes. Despite these well-established roles, such information has yet to be exploited for drug design. Here we show by nuclear magnetic resonance spectroscopy that inhibitors LpxC—an essential the lipid A biosynthetic pathway Gram-negative bacteria a validated novel antibiotic target—access alternative, minor population states solution...