Scholars@Duke
Eric John Toone

Eric John Toone

Professor Emeritus of Chemistry
Chemistry
eric.toone@duke.edu
Box 90346, Durham, NC 27708-0346
3236 French Science Center, Durham, NC 27708

Selected Publications

Preclinical safety and efficacy characterization of an LpxC inhibitor against Gram-negative pathogens.

Journal Article Sci Transl Med · August 9, 2023 The UDP-3-O-(R-3-hydroxyacyl)-N-acetylglucosamine deacetylase LpxC is an essential enzyme in the biosynthesis of lipid A, the outer membrane anchor of lipopolysaccharide and lipooligosaccharide in Gram-negative bacteria. The development of LpxC-targeting a ... Full text Link to item Cite

Degradation of Components of the Lpt Transenvelope Machinery Reveals LPS-Dependent Lpt Complex Stability in Escherichia coli.

Journal Article Front Mol Biosci · 2021 Lipopolysaccharide (LPS) is a peculiar component of the outer membrane (OM) of many Gram-negative bacteria that renders these bacteria highly impermeable to many toxic molecules, including antibiotics. LPS is assembled at the OM by a dedicated intermembran ... Full text Open Access Link to item Cite

Curative Treatment of Severe Gram-Negative Bacterial Infections by a New Class of Antibiotics Targeting LpxC.

Journal Article mBio · July 25, 2017 The infectious diseases caused by multidrug-resistant bacteria pose serious threats to humankind. It has been suggested that an antibiotic targeting LpxC of the lipid A biosynthetic pathway in Gram-negative bacteria is a promising strategy for curing Gram- ... Full text Open Access Link to item Cite

High susceptibility of MDR and XDR Gram-negative pathogens to biphenyl-diacetylene-based difluoromethyl-allo-threonyl-hydroxamate LpxC inhibitors.

Journal Article J Antimicrob Chemother · October 2016 OBJECTIVES: Inhibitors of uridine diphosphate-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC, which catalyses the first, irreversible step in lipid A biosynthesis) are a promising new class of antibiotics against Gram-negative bacteria. T ... Full text Open Access Link to item Cite

A Scalable Synthesis of the Difluoromethyl-allo-threonyl Hydroxamate-Based LpxC Inhibitor LPC-058.

Journal Article J Org Chem · May 20, 2016 The difluoromethyl-allo-threonyl hydroxamate-based compound LPC-058 is a potent inhibitor of UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) in Gram-negative bacteria. A scalable synthesis of this compound is described. The key step i ... Full text Open Access Link to item Cite

Drug design from the cryptic inhibitor envelope.

Journal Article Nat Commun · February 25, 2016 Conformational dynamics plays an important role in enzyme catalysis, allosteric regulation of protein functions and assembly of macromolecular complexes. Despite these well-established roles, such information has yet to be exploited for drug design. Here w ... Full text Open Access Link to item Cite

Specific binding at the cellulose binding module-cellulose interface observed by force spectroscopy.

Journal Article Langmuir : the ACS journal of surfaces and colloids · March 2015 The need for effective enzymatic depolymerization of cellulose has stimulated an interest in interactions between protein and cellulose. Techniques utilized for quantitative measurements of protein-cellulose noncovalent association include microgravimetry, ... Full text Cite

Diamond surface functionalization with biomimicry - Amine surface tether and thiol moiety for electrochemical sensors

Journal Article Applied Surface Science · May 15, 2014 The surface of conducting diamond was functionalized with a terminal thiol group that is capable of binding and detecting nitrogen-oxygen species. The functionalization process employed multiple steps starting with doped diamond films grown by plasma enhan ... Full text Cite

Structural Modifications in Bilayered Molecular Systems Lead to Predictable Changes in Their Electronic Properties

Journal Article Advanced Materials Interfaces · April 1, 2014 This study uses a novel surface engineering approach to demonstrate the influence of organic functional group substitutions on molecular electronic properties. Specifically, bilayered organic monomolecular systems immobilized on an inorganic electrode as t ... Full text Cite

Structural basis of the promiscuous inhibitor susceptibility of Escherichia coli LpxC.

Journal Article ACS Chem Biol · January 17, 2014 The LpxC enzyme in the lipid A biosynthetic pathway is one of the most promising and clinically unexploited antibiotic targets for treatment of multidrug-resistant Gram-negative infections. Progress in medicinal chemistry has led to the discovery of potent ... Full text Link to item Cite

Photo-activated psoralen binds the ErbB2 catalytic kinase domain, blocking ErbB2 signaling and triggering tumor cell apoptosis.

Journal Article PLoS One · 2014 Photo-activation of psoralen with UVA irradiation, referred to as PUVA, is used in the treatment of proliferative skin disorders. The anti-proliferative effects of PUVA have been largely attributed to psoralen intercalation of DNA, which upon UV treatment, ... Full text Link to item Cite

Synthesis, structure, and antibiotic activity of aryl-substituted LpxC inhibitors.

Journal Article J Med Chem · September 12, 2013 The zinc-dependent deacetylase LpxC catalyzes the committed step of lipid A biosynthesis in Gram-negative bacteria and is a validated target for the development of novel antibiotics to combat multidrug-resistant Gram-negative infections. Many potent LpxC i ... Full text Link to item Cite

Effect of compressive force on unbinding specific protein-ligand complexes with force spectroscopy.

Journal Article The journal of physical chemistry. B · May 2013 Atomic force microscopy (AFM) is used extensively for the investigation of noncovalent molecular association. Although the technique is used to derive various types of information, in almost all instances the frequency of complex formation, the magnitude o ... Full text Cite

Enthalpic signature of methonium desolvation revealed in a synthetic host-guest system based on cucurbit[7]uril.

Journal Article Journal of the American Chemical Society · April 2013 Methonium (N(+)Me3) is an organic cation widely distributed in biological systems. As an organic cation, the binding of methonium to protein receptors requires the removal of a positive charge from water. The appearance of methonium in biological transmitt ... Full text Cite

An enthalpic basis of additivity in biphenyl hydroxamic acid ligands for stromelysin-1.

Journal Article Bioorganic & medicinal chemistry letters · October 2012 Fragment based drug discovery remains a successful tool for pharmaceutical lead discovery. Although based upon the principle of thermodynamic additivity, the underlying thermodynamic basis is poorly understood. A thermodynamic additivity analysis was perfo ... Full text Cite

A general and efficient cantilever functionalization technique for AFM molecular recognition studies.

Journal Article Biopolymers · October 2012 Atomic force microscopy (AFM) is a versatile technique for the investigation of noncovalent molecular associations between ligand-substrate pairs. Surface modification of silicon nitride AFM cantilevers is most commonly achieved using organic trialkoxysila ... Full text Cite

Multicomponent patterning of indium tin oxide.

Journal Article ACS applied materials & interfaces · August 2012 We report a versatile functionalization and pattering technique that permits multicomponent pattern-specific modification of indium tin oxide (ITO) with organic species. The method relies on a bilayered molecular system that simultaneously protects ITO fro ... Full text Cite

Improving upon nature: active site remodeling produces highly efficient aldolase activity toward hydrophobic electrophilic substrates.

Journal Article Biochemistry · February 2012 The substrate specificity of enzymes is frequently narrow and constrained by multiple interactions, limiting the use of natural enzymes in biocatalytic applications. Aldolases have important synthetic applications, but the usefulness of these enzymes is ha ... Full text Cite

Modulation of Wnt/β-catenin signaling and proliferation by a ferrous iron chelator with therapeutic efficacy in genetically engineered mouse models of cancer.

Journal Article Oncogene · January 12, 2012 Using a screen for Wnt/β-catenin inhibitors, a family of 8-hydroxyquinolone derivatives with in vivo anti-cancer properties was identified. Analysis of microarray data for the lead compound N-((8-hydroxy-7-quinolinyl) (4-methylphenyl)methyl)benzamide (HQBA ... Full text Link to item Cite

Preface

Other Smith's Textbook of Endourology: 3rd Edition · January 5, 2012 Full text Cite

Derivatives of plant phenolic compound affect the type III secretion system of Pseudomonas aeruginosa via a GacS-GacA two-component signal transduction system.

Journal Article Antimicrobial agents and chemotherapy · January 2012 Antibiotic therapy is the most commonly used strategy to control pathogenic infections; however, it has contributed to the generation of antibiotic-resistant bacteria. To circumvent this emerging problem, we are searching for compounds that target bacteria ... Full text Cite

Soft lithographic functionalization and patterning oxide-free silicon and germanium.

Journal Article Journal of visualized experiments : JoVE · December 2011 The development of hybrid electronic devices relies in large part on the integration of (bio)organic materials and inorganic semiconductors through a stable interface that permits efficient electron transport and protects underlying substrates from oxidati ... Full text Cite

Preface

Book · December 1, 2011 Cite

Exploring variation in binding of Protein A and Protein G to immunoglobulin type G by isothermal titration calorimetry.

Journal Article Journal of molecular recognition : JMR · November 2011 Bacterial Protein A (PrtA) and Protein G (PrtG) are widely used for affinity purification of antibodies. An understanding of how PrtA and PrtG bind to different isotypes of immunoglobulin type G (IgG) and to their corresponding Fc fragments is essential fo ... Full text Cite

Directed evolution of a pyruvate aldolase to recognize a long chain acyl substrate.

Journal Article Bioorganic & medicinal chemistry · November 2011 The use of biological catalysts for industrial scale synthetic chemistry is highly attractive, given their cost effectiveness, high specificity that obviates the need for protecting group chemistry, and the environmentally benign nature of enzymatic proced ... Full text Cite

Advances in Enzymology and Related Areas of Molecular Biology

Book · October 14, 2011 This book covers important advances in enzymology, explaining the behavior of enzymes and how they can be utilized to develop novel drugs, synthesize known and novel compounds, and understand evolutionary processes. Advances in Enzymology focuses on enzyme ... Full text Cite

A multidisciplinary approach to probing enthalpy-entropy compensation and the interfacial mobility model.

Journal Article Journal of the American Chemical Society · August 2011 In recent years, interfacial mobility has gained popularity as a model with which to rationalize both affinity in ligand binding and the often observed phenomenon of enthalpy-entropy compensation. While protein contraction and reduced mobility, as demonstr ... Full text Cite

Lipooligosaccharide is required for the generation of infectious elementary bodies in Chlamydia trachomatis.

Journal Article Proc Natl Acad Sci U S A · June 21, 2011 Lipopolysaccharides (LPS) and lipooligosaccharides (LOS) are the main lipid components of bacterial outer membranes and are essential for cell viability in most Gram-negative bacteria. Here we show that small molecule inhibitors of LpxC [UDP-3-O-(R-3-hydro ... Full text Link to item Cite

Soft-lithographic approach to functionalization and nanopatterning oxide-free silicon.

Journal Article Langmuir : the ACS journal of surfaces and colloids · May 2011 We report a simple, reliable high-throughput method for patterning passivated silicon with reactive organic monolayers and demonstrate selective functionalization of the patterned substrates with both small molecules and proteins. The approach completely p ... Full text Cite

Patterning NHS-terminated SAMs on germanium.

Journal Article Langmuir : the ACS journal of surfaces and colloids · May 2011 Here we report a simple, robust approach to patterning functional SAMs on germanium. The protocol relies on catalytic soft-lithographic pattern transfer from an elastomeric stamp bearing pendant immobilized sulfonic acid moieties to an NHS-functionalized b ... Full text Cite

Advances in Enzymology and Related Areas of Molecular Biology

Book · February 24, 2011 This book covers important advances in enzymology, explaining the behavior of enzymes and how they can be utilized to develop novel drugs, synthesize known and novel compounds, and understand evolutionary processes. ... Full text Cite

Thermodynamic characterization of the binding interaction between the histone demethylase LSD1/KDM1 and CoREST.

Journal Article Biochemistry · February 2011 Flavin-dependent histone demethylases catalyze the posttranslational oxidative demethylation of mono- and dimethylated lysine residues, producing formaldehyde and hydrogen peroxide in addition to the corresponding demethylated protein. In vivo, histone dem ... Full text Cite

Species-specific and inhibitor-dependent conformations of LpxC: implications for antibiotic design.

Journal Article Chem Biol · January 28, 2011 LpxC is an essential enzyme in the lipid A biosynthetic pathway in gram-negative bacteria. Several promising antimicrobial lead compounds targeting LpxC have been reported, though they typically display a large variation in potency against different gram-n ... Full text Link to item Cite

Syntheses, structures and antibiotic activities of LpxC inhibitors based on the diacetylene scaffold.

Journal Article Bioorg Med Chem · January 15, 2011 Compounds inhibiting LpxC in the lipid A biosynthetic pathway are promising leads for novel antibiotics against multidrug-resistant Gram-negative pathogens. We report the syntheses and structural and biochemical characterizations of LpxC inhibitors based o ... Full text Link to item Cite

Advances in enzymology and related areas of molecular biology. Preface.

Journal Article Advances in enzymology and related areas of molecular biology · January 2011 Cite

Bacterial infection remains a leading cause of death in both Western and developing world. Preface.

Journal Article Advances in enzymology and related areas of molecular biology · January 2011 Cite

Preface

Chapter · 2011 Full text Cite

Advances in Enzymology: And Related Areas of Molecular Biology

Book · May 3, 2010 Advances in Enzymology and Related Areas of Molecular Biology covers the advances in enzymology, explaining the behavior of enzymes and how they can be utilized to develop novel drugs, synthesize known and novel compounds, and understand evolutionary proce ... Full text Cite

Identification and inhibitory properties of a novel Ca(2+)/calmodulin antagonist.

Journal Article Biochemistry · May 2010 We developed a high-throughput yeast-based assay to screen for chemical inhibitors of Ca(2+)/calmodulin-dependent kinase pathways. After screening two small libraries, we identified the novel antagonist 125-C9, a substituted ethyleneamine. In vitro kinase ... Full text Open Access Cite

Catalytic microcontact printing on chemically functionalized H-terminated silicon.

Journal Article Langmuir : the ACS journal of surfaces and colloids · February 2010 We report a novel inkless soft lithographic fabrication protocol that permits uniform parallel patterning of hydrogen-terminated silicon surfaces using catalytic elastomeric stamps. Pattern transfer is achieved catalytically via reaction between sulfonic a ... Full text Open Access Cite

A single step purification for autolytic zinc proteinases.

Journal Article Bioorganic & medicinal chemistry letters · January 2010 We describe a novel single-step method for the purification of stromelysin-1 catalytic domain (SCD) via immobilized metal affinity chromatography under denaturing conditions that inhibit proteolytic activity followed by on-column refolding and spontaneous ... Full text Cite

Inkless microcontact printing on SAMs of Boc- and TBS-protected thiols.

Journal Article Nano letters · January 2010 We report a new inkless catalytic muCP technique that achieves accurate, fast, and complete pattern reproduction on SAMs of Boc- and TBS-protected thiols immobilized on gold using a polyurethane-acrylate stamp functionalized with covalently bound sulfonic ... Full text Open Access Cite

Forcing a closer look

Journal Article Biopolymers · January 1, 2010 Full text Cite

Minimizing tip-sample contact force in automated atomic force microscope based force spectroscopy

Journal Article Proceedings of the ASME Design Engineering Technical Conference · December 1, 2009 In atomic force microscope based force spectroscopy, it is often necessary to minimize the tip-sample contact force. While it is possible to control the contact force using force feedback, this method is susceptible to sensor drift and is often underutiliz ... Full text Cite

In situ growth of a stoichiometric PEG-like conjugate at a protein's N-terminus with significantly improved pharmacokinetics.

Journal Article Proc Natl Acad Sci U S A · September 8, 2009 The challenge in the synthesis of protein-polymer conjugates for biological applications is to synthesize a stoichiometric (typically 1:1) conjugate of the protein with a monodisperse polymer, with good retention of protein activity, significantly improved ... Full text Link to item Cite

Eyedrops containing SA9000 prodrugs result in sustained reductions in intraocular pressure in rabbits.

Journal Article J Ocul Pharmacol Ther · June 2009 AIM: Poor topical bioavailability and ocular irritation have impeded the development of the diuretic, ethacrynic acid (ECA) as a clinically useful ocular hypotensive for the treatment of glaucoma. Thus, the development of analogs and prodrugs of analogs wi ... Full text Link to item Cite

C-nitroso donors of nitric oxide.

Journal Article The Journal of organic chemistry · February 2009 A complete understanding of the biological activity of nitric oxide (NO) is complicated by the different reactivity profiles of its various species and by the often complex decomposition behavior of the NO progenitors in common use. Here, we report that ap ... Full text Cite

Natural product glycosyltransferases: properties and applications.

Journal Article Advances in enzymology and related areas of molecular biology · January 2009 Full text Cite

Advances in enzymology and related areas of molecular biology. Preface.

Journal Article Advances in enzymology and related areas of molecular biology · January 2009 Cite

Advances in enzymology and related areas of molecular biology

Book · September 29, 2008 Natural products continue to play an important role in the treatment of human disease. Among the most daunting limitations to the use of such species is the need for synthetic approaches to the significant quantities of material needed for biochemical stud ... Full text Cite

Identification of chemical inhibitors to human tissue transglutaminase by screening existing drug libraries.

Journal Article Chem Biol · September 22, 2008 Human tissue transglutaminase (TGM2) is a calcium-dependent crosslinking enzyme involved in the posttranslational modification of intra- and extracellular proteins and implicated in several neurodegenerative diseases. To find specific inhibitors to TGM2, t ... Full text Link to item Cite

Characterization and crystal structure of Escherichia coli KDPGal aldolase.

Journal Article Bioorganic & medicinal chemistry · January 2008 2-Keto-3-deoxy-6-phosphogluconate (KDPG) and 2-keto-3-deoxy-6-phosphogalactonate (KDPGal) aldolases catalyze an identical reaction differing in substrate specificity in only the configuration of a single stereocenter. However, the proteins show little sequ ... Full text Cite

Mutagenesis of the phosphate-binding pocket of KDPG aldolase enhances selectivity for hydrophobic substrates.

Journal Article Protein science : a publication of the Protein Society · November 2007 Narrow substrate specificities often limit the use of enzymes in biocatalysis. To further the development of Escherichia coli 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase as a biocatalyst, the molecular determinants of substrate specificity were probe ... Full text Cite

Inkless microcontact printing on self-assembled monolayers of fmoc-protected aminothiols.

Journal Article Journal of the American Chemical Society · November 2007 Full text Cite

Biocatalytic microcontact printing.

Journal Article The Journal of organic chemistry · September 2007 Immobilized biocatalytic lithography is presented as an application of soft lithography. In traditional microcontact printing, diffusion limits resolution of pattern transfer. By using an immobilized catalyst, the lateral resolution of microcontact printin ... Full text Cite

Practical synthesis of fully protected globotriaose and its glycopolymers

Journal Article Carbohydrate Polymers · June 1, 2007 Convenient and useful construction of a trisaccharide moiety of globotriaosyl ceramide was performed by means of modified Ogawa's protocol. In order to evaluate an efficiency of new class of glycopolymers, further chemical transformations of the trisacchar ... Full text Cite

A stochastic, cantilever approach to the evaluation of solution phase thermodynamic quantities.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · February 2007 A cantilever device based on competitive binding of an immobilized receptor to immobilized and soluble ligand and capable of measuring solution-phase thermodynamic quantities is described. Through multiple binary queries, the device stochastically measures ... Full text Cite

Pyruvate aldolases in chiral carbon-carbon bond formation.

Journal Article Nature protocols · January 2007 A procedure for the preparation of optically pure alpha-keto-gamma-hydroxy carboxylic acids through stereospecific aldol addition catalyzed by pyruvate aldolases from the Entner-Doudoroff and the DeLey-Doudoroff glycolytic pathways is described. This highl ... Full text Cite

Preface

Journal Article Cardiothoracic Critical Care · January 1, 2007 Full text Cite

Binding of warfarin influences the acid-base equilibrium of H242 in sudlow site I of human serum albumin.

Journal Article Photochemistry and photobiology · September 2006 Sudlow Site I of human serum albumin (HSA) is located in subdomain IIA of the protein and serves as a binding cavity for a variety of ligands. In this study, the binding of warfarin (W) is examined using computational techniques and isothermal titration ca ... Full text Cite

Mechanism of the Class I KDPG aldolase.

Journal Article Bioorganic & medicinal chemistry · May 2006 In vivo, 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase catalyzes the reversible, stereospecific retro-aldol cleavage of KDPG to pyruvate and D-glyceraldehyde-3-phosphate. The enzyme is a lysine-dependent (Class I) aldolase that functions through the in ... Full text Cite

A droplet-based lab-on-a-chip for colorimetric detection of nitroaromatic explosives

Journal Article Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS) · October 25, 2005 Portable and automated field screening equipment would be very effective in detecting and quantifying explosives at various sites. A droplet-based microfluidic lab-on-a-chip utilizing electrowetting is presented for the colorimetric detection of TNT (trini ... Full text Cite

Nitrosonium-catalyzed decomposition of s-nitrosothiols in solution: a theoretical and experimental study.

Journal Article Journal of the American Chemical Society · August 2005 The decomposition of S-nitrosothiols (RSNO) in solution under oxidative conditions is significantly faster than can be accounted for by homolysis of the S-N bond. Here we propose a cationic chain mechanism in which nitrosation of nitrosothiol produces a ni ... Full text Cite

A small-molecule inhibitor of isoprenylcysteine carboxyl methyltransferase with antitumor activity in cancer cells.

Journal Article Proc Natl Acad Sci U S A · March 22, 2005 Many key regulatory proteins, including members of the Ras family of GTPases, are modified at their C terminus by a process termed prenylation. This processing is initiated by the addition of an isoprenoid lipid, and the proteins are further modified by a ... Full text Link to item Cite

Synthesis of carbosilane dendrimers having peripheral mannose and mannobiose

Journal Article Tetrahedron · March 14, 2005 The mannose monosaccharide derivative, acetylthiopropyl 2,3,4,6-tetra-O-acetyl-α-d-mannopyranoside (Man), and the mannobiose derivative, acetylthiopropyl 2,4,6-tri-O-acetyl-3-O-(2′,3′,4′, 6′-tetra-O-acetyl-α-d-mannopyranosyl)-α-d-mannopyranoside (α-1,3-Man ... Full text Cite

C-nitroso compounds: synthesis, physicochemical properties and biological activities.

Journal Article Current topics in medicinal chemistry · January 2005 Because of the chemical and physical properties of nitric oxide, its effective use and delivery for therapeutic application represents a significant challenge. Accordingly, current understanding of nitric oxide biology largely stems from the use of nitric ... Full text Cite

Quantitative determination of analytes by force microscopy

Journal Article J. Am. Chem. Soc. · 2005 Cite

A bacterial selection for the directed evolution of pyruvate aldolases.

Journal Article Bioorganic & medicinal chemistry · August 2004 A novel bacterial in vivo selection for pyruvate aldolase activity is described. Pyruvate kinase deficient cells, which lack the ability to biosynthetically generate pyruvate, require supplementation of exogenous pyruvate when grown on ribose. Supplementat ... Full text Cite

Binding of ochratoxin a to human serum albumin stabilized by a protein-ligand ion pair

Journal Article Journal of Physical Chemistry B · August 7, 2003 Ochratoxin A (OTA), a fungal metabolite of strains of Penicillium and Aspergillus, binds in its dianion form to Sudlow site I of human serum albumin (HSA) with high affinity. In this study, isothermal calorimetry (ITC) is used to study the binding of OTA a ... Full text Cite

Solid-phase synthesis for the identification of high-affinity bivalent lectin ligands.

Journal Article The Journal of organic chemistry · July 2003 The development of carbohydrate-based therapeutics has been frustrated by the low affinities that characterize protein-carbohydrate complexation. Because of the oligomeric nature of most lectins, the use of multivalency may offer a successful strategy for ... Full text Cite

Additivity and the physical basis of multivalency effects: a thermodynamic investigation of the calcium EDTA interaction.

Journal Article Journal of the American Chemical Society · June 2003 To better understand the origin of multivalency effects in ligand binding, the binding of a series of mono-, bi-, tri- and tetravalent carboxylate ligands to Ca(II) was examined by isothermal titration calorimetry (ITC). The data are inconsistent with an e ... Full text Cite

Nitroxyl disulfides, novel intermediates in transnitrosation reactions.

Journal Article Journal of the American Chemical Society · June 2003 A novel anionic RSN(O)SR species, the intermediate in transnitrosation reactions, was explored computationally with B3LYP and CBS-QB3 methods. The species resembles a nitroxyl coordinated to a highly distorted disulfide, and it differs significantly from i ... Full text Cite

Calorimetric evaluation of protein-carbohydrate affinities.

Journal Article Methods in enzymology · January 2003 Full text Cite

Towards high affinity carbohydrate-binding proteins: Directed evolution of murine galectin-3

Journal Article Canadian Journal of Chemistry · December 3, 2002 Towards a better understanding of the molecular basis of affinity, a directed evolution of murine galectin-3 (G3) was initiated to produce mutants with improved affinity for lactose and N-acetyllactosamine relative to the wild-type protein. A series of N-t ... Full text Cite

The decomposition of thionitrites.

Journal Article Current opinion in chemical biology · December 2002 The mechanism of thionitrite decomposition, both in vivo and in vitro, remains unclear. Thionitrite stability is highly variable; it is a complex function of thionitrite structure and environmental condition. Several recent advances clarify the role of uni ... Full text Cite

Analysis of S-nitrosothiol decomposition

Journal Article Proceedings 50th ASMS Conference on Mass Spectrometry and Allied Topics · December 1, 2002 The fate of various low molecular weight RSNO compounds under different conditions were studied by employing an Agilent 1100 LC/MCD ion trap. Electrospray ionization (ESI) was utilized and ion were detected in the negative ion mode with the expectation of ... Cite

Cloning, isolation and characterization of the Thermotoga maritima KDPG aldolase.

Journal Article Bioorganic & medicinal chemistry · March 2002 The Thermotoga maritima aldolase gene has been cloned into a T7 expression vector and overexpressed in Escherichia coli. The preparation yields 470 UL(-1) of enzyme at a specific activity of 9.4 U mg(-1). During retroaldol cleavage of KDPG, the enzyme show ... Full text Cite

The cluster glycoside effect.

Journal Article Chemical reviews · February 2002 Full text Cite

S-N dissociation energies of S-nitrosothiols: on the origins of nitrosothiol decomposition rates.

Journal Article Journal of the American Chemical Society · September 2001 Full text Cite

S-nitrosothiol repletion by an inhaled gas regulates pulmonary function.

Journal Article Proc Natl Acad Sci U S A · May 8, 2001 NO synthases are widely distributed in the lung and are extensively involved in the control of airway and vascular homeostasis. It is recognized, however, that the O(2)-rich environment of the lung may predispose NO toward toxicity. These Janus faces of NO ... Full text Link to item Cite

Thermodynamics of metal ion binding. 1. Metal ion binding by wild-type carbonic anhydrase.

Journal Article Biochemistry · May 2001 Understanding the energetic consequences of molecular structure in aqueous solution is a prerequisite to the rational design of synthetic motifs with predictable properties. Such properties include ligand binding and the collapse of polymer chains into dis ... Full text Cite

Thermodynamics of metal ion binding. 2. Metal ion binding by carbonic anhydrase variants.

Journal Article Biochemistry · May 2001 The ability to construct molecular motifs with predictable properties in aqueous solution requires an extensive knowledge of the relationships between structure and energetics. The design of metal binding motifs is currently an area of intense interest in ... Full text Cite

Directed evolution of a new catalytic site in 2-keto-3-deoxy-6-phosphogluconate aldolase from Escherichia coli.

Journal Article Structure (London, England : 1993) · January 2001 BackgroundAldolases are carbon bond-forming enzymes that have long been identified as useful tools for the organic chemist. However, their utility is limited in part by their narrow substrate utilization. Site-directed mutagenesis of various enzym ... Full text Cite

Multivalency effects in protein--carbohydrate interaction: the binding of the Shiga-like toxin 1 binding subunit to multivalent C-linked glycopeptides.

Journal Article The Journal of organic chemistry · December 2000 A series of monovalent and bivalent glycopeptides displaying a C-linked analogue of the Pk trisaccharide, the in vivo ligand for the pentavalent Shiga-like toxin binding subunit (SLT-1B), were prepared and evaluated as ligands for SLT-1B by isothermal titr ... Full text Cite

Microcalorimetric determination of thermodynamic parameters for ionophore-siderophore host-guest complex formation.

Journal Article Inorganic chemistry · March 2000 Thermodynamic parameters (delta H, delta S, and delta G) were determined by microcalorimetry in wet chloroform for host-guest assembly formation involving second-sphere complexation of the siderophore ferrioxamine B by crown ether (18-crown-6, cis-dicycloh ... Full text Cite

Regioselective reduction of 4,6-O-benzylidenes using triethylsilane and BF3.Et2O

Journal Article Tetrahedron Asymmetry · February 11, 2000 The 4,6-di-O-benzylidene acetals of glucose, mannose, glucosamine, and galactose were regioselectively reduced by triethylsilane in the presence of BF3.Et2O to yield the 6-O-benzyl ethers in good to excellent yields. Copyright (C) 2000 Elsevier Science Ltd ... Full text Cite

Enzyme-catalyzed synthesis of carbohydrates.

Journal Article Current opinion in chemical biology · February 2000 Several new enzymes of utility in the synthesis of carbohydrates have been reported during the past year. Additionally, the utility of several well studied enzymes has been expanded. Pyruvate aldolases, aldolase abzymes and both wild-type and mutated glyco ... Full text Cite

A comparison of biological and calorimetric analyses of multivalent glycodendrimer ligands for concanavalin A

Journal Article Tetrahedron Asymmetry · January 28, 2000 The cluster glycoside effect - the observation that multivalent glycosides bind to their polyvalent protein receptors with apparent affinities greater than those that can be rationalized solely on the basis of valency - is by now a well established phenome ... Full text Cite

Enzymatic Carbohydrate Synthesis

Journal Article Current Opinion in Chemical Biology · 2000 Cite

Synthesis of α- and β-carbon-linked serine analogues of the P(k) trisaccharide

Journal Article Journal of Organic Chemistry · December 10, 1999 The synthesis of glycopeptide ligands for a range of biomedically relevant carbohydrate-binding proteins is a topic of great importance to the glycobiology community. This task is impeded by the inherent instability of glycosyl linkages to serine/threonine ... Full text Cite

On the meaning of affinity: Cluster glycoside effects and concanavalin A

Journal Article Journal of the American Chemical Society · November 10, 1999 The inhibition of protein-carbohydrate interaction provides a powerful therapeutic strategy for the treatment of myriad human diseases. To date, application of such approaches have been frustrated by the inherent low affinity of carbohydrate ligands for th ... Full text Cite

Initiating a structural study of 2-keto-3-deoxy-6-phosphogluconate aldolase from Escherichia coli.

Journal Article Acta crystallographica. Section D, Biological crystallography · November 1999 2-Keto-3-deoxy-6-phosphogluconate aldolase (KDPG aldolase, E.C. 4.1. 2.14) is a member of the pyruvate/phosphoenolpyruvate aldolase family. It is also a synthetically useful enzyme, capable of catalyzing the stereoselective aldol addition of pyruvate to a ... Full text Cite

The synthetic utility of KDPGal aldolase

Journal Article Journal of Molecular Catalysis - B Enzymatic · September 15, 1998 We describe the isolation and purification of KDPGal aldolase from two sources. To facilitate this isolation, a facile five-step chemical synthesis of 2-keto-3-deoxy-6-phosphogalactonate (KDPGal) (1) from commercially available D-galactono-1,4-lactone (3) ... Full text Cite

Crystallization of succinylated concanavalin A bound to a synthetic bivalent ligand and preliminary structural analysis.

Journal Article Acta crystallographica. Section D, Biological crystallography · September 1998 Crystals have been obtained of succinylated concanavalin A complexed to a novel bidentate synthetic ligand. The crystals are the first example of a lectin with a synthetic multivalent ligand and the first report of crystallization of succinylated concanava ... Full text Cite

Effect of phosphorylation on the reaction rate of unnatural electrophiles with 2-keto-3-deoxy-6-phosphogluconate aldolase

Journal Article Journal of the Chemical Society - Perkin Transactions 1 · April 7, 1998 D-Glyceraldehyde is accepted as an electrophile by 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase (EC 4.1.2.14) at 1% the rate of natural substrate, D-glyceraldehyde 3-phosphate. Accordingly, it was expected that addition of a phosphate moiety at C3 or ... Full text Cite

Phosphate as Both a Activating and Protecting Group in Aldolase-Based Syntheses

Journal Article J. Chem. Soc. Perkin Trans. I · 1998 Cite

Exploring the basis of peptide-carbohydrate crossreactivity: evidence for discrimination by peptides between closely related anti-carbohydrate antibodies.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · March 1997 To investigate the molecular basis of antigenic mimicry by peptides, we studied a panel of closely related mAbs directed against the cell-wall polysaccharide of group A Streptococcus. These antibodies have restricted V-gene usage, indicating a shared mecha ... Full text Cite

(S)NO Signals: A Consensus Motif

Journal Article Neuron · 1997 Cite

Synthesis of carbon-linked glycopeptides through catalytic asymmetric hydrogenation

Journal Article Journal of the American Chemical Society · January 1, 1997 Full text Cite

A comparison of the fine saccharide-binding specificity of Dioclea grandiflora lectin and concanavalin A.

Journal Article European journal of biochemistry · December 1996 The lectin from the seeds of Dioclea grandiflora (DGL) is a Man/Glc-specific tetrameric protein with physical and saccharide-binding properties reported to be similar to that of the jack bean lectin concanavalin A (ConA). Unlike other plant lectins, both D ... Full text Cite

2-keto-3-deoxy-6-phosphogluconate aldolases as catalysts for stereocontrolled carbon-carbon bond formation

Journal Article Journal of the American Chemical Society · December 1, 1996 The pyruvate aldolases use pyruvate as the nucleophilic component in stereoselective aldol condensations, producing a 4-hydroxy-2-ketobutyrate framework. We have examined the 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolases from Pseudomonas putida, Esche ... Cite

Analysis of the binding specificities of oligomannoside-binding proteins using methylated monosaccharides.

Journal Article Bioorganic & medicinal chemistry · November 1996 The binding specificities of the closely related lectins from Canavalia ensiformis and Dioclea grandiflora were examined using specifically O-alkylated mono- and disaccharides. Both lectins accept any substitution at the monosaccharide C2 hydroxyl group. T ... Full text Cite

Specificity of C-glycoside complexation by mannose/glucose specific lectins.

Journal Article Biochemistry · March 1996 The binding of the mannose/glucose specific lectins from Canavalia ensiformis (concanavalin A) and Dioclea grandiflora to a series of C-glucosides were studied by titration microcalorimetry and fluorescence anisotropy titration. These closely related lecti ... Full text Cite

Phenylalanine 30 plays an important role in receptor binding of verotoxin-1.

Journal Article Molecular microbiology · February 1996 The homopentameric B subunit of verotoxin 1 (VT1) binds to the glycosphingolipid receptor globotriaosylceramide (Gb3). We produced mutants with alanine substitutions for residues found near the cleft between adjacent subunits. Substitution of alanine for p ... Full text Cite

2-Keto-3-deoxy-6-phosphogluconate aldolases as catalysts for stereocontrolled carbon-carbon bond formation

Journal Article Journal of the American Chemical Society · January 1, 1996 The pyruvate aldolases use pyruvate as the nucleophilic component in stereoselective aldol condensations, producing a 4-hydroxy-2-ketobutyrate framework. We have examined the 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolases from Pseudomonas putida, Esche ... Full text Cite

Calorimetric analysis of the binding of lectins with overlapping carbohydrate-binding ligand specificities.

Journal Article Biochemistry · April 1995 The thermodynamics of binding of a system of plant lectins specific for the oligosaccharide methyl 3,6-di-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside have been studied calorimetrically. This system of lectins consists of concanavalin A, the lectin i ... Full text Cite

Differential dye-ligand chromatography as a general purification protocol for 2-keto-3-deoxy-6-phosphogluconate aldolases

Journal Article Tetrahedron: Asymmetry · January 1, 1995 2-Keto-3-deoxy-6-phosphogluconate aldolases (KDPG aldolases, EC 4.1.2.14) from four sources, Esherichia coli, Pseudomonas putida, Pseudomonas saccharophila, and Zymononas mobilis, were purified from 17- to 48- fold by differential dye-ligand chromatography ... Full text Cite

Interaction of the Shiga-like toxin type 1 B-subunit with its carbohydrate receptor.

Journal Article Biochemistry · December 1994 A study of the binding of the Shiga-like toxin 1 (SLT-1) to the P(k) trisaccharide [methyl 4-O-(4-O-alpha-D-galactopyranosyl)-4-O-beta-D- glucopyranoside] and its constituent dissacharides was carried out. The trisaccharide represents the carbohydrate reco ... Full text Cite

A Direct Measure of the Contribution of Solvent Reorganization to the Enthalpy of Binding

Journal Article Journal of the American Chemical Society · November 1, 1994 The thermodynamics of association of several binding systems, including protein—carbohydrate, small molecule—small molecule, protein—peptide, and protein—nucleic acid, were evaluated calorimetrically in light and heavy water. In every case, the enthalpy of ... Full text Cite

Increased adhesion between neutral lipid bilayers: interbilayer bridges formed by tannic acid.

Journal Article Biophys J · June 1994 Tannic acid (TA) is a naturally occurring polyphenolic compound that aggregates membranes and neutral phosolipid vesicles and precipitates many proteins. This study analyzes TA binding to lipid membranes and the ensuing aggregation. The optical density of ... Full text Link to item Cite

Preface

Chapter · January 1, 1994 Full text Cite

Structure and energetics of protein-carbohydrate complexes

Journal Article Current Opinion in Structural Biology · January 1, 1994 During the past year, several new coordinate sets for protein-carbohydrate complexes have appeared. The data fall into two important categories: complexes of lectins other than legume and chemotaxis proteins, and high-resolution refinements that allow plac ... Full text Cite

Calorimetric Evaluation of Enzyme Kinetic Parameters

Journal Article Journal of Organic Chemistry · January 1, 1993 The measurement of kinetic parameters (kcat, Km, Ki) for a wide range of proteolytic enzymes is vital to contemporary bioorganic and medicinal chemistry. Enzyme assays based on changes in optical properties of the system or changes in concentration of an i ... Full text Cite

Energetics of lectin-carbohydrate binding. A microcalorimetric investigation of concanavalin A-oligomannoside complexation.

Journal Article The Journal of biological chemistry · November 1992 Despite years of study, a comprehensive picture of the binding of the lectin from Canavalia ensiformis, concanavalin A, to carbohydrates remains elusive. We report here studies on the interaction of concanavalin A with methyl 3,6-di-O-(alpha-D-mannopyranos ... Full text Cite

Pyruvate Aldolases as Reagents for Stereospecific Aldol Condensation

Journal Article Journal of Organic Chemistry · January 1, 1992 KDPG aldolase, a representative member of the largest but as of yet unexplored group of aldolases which utilize pyruvate as the nucleophilic component in aldol condensation, accepts a number of unnatural aldehydes as electrophiles in stereospecific aldol c ... Full text Cite

Preface

Journal Article Solar Energy Materials · December 1, 1991 Full text Cite

Enzymatic Synthesis of Uridine 5′-Diphosphoglucuronic Acid on a Gram Scale

Journal Article Journal of Organic Chemistry · September 1, 1991 A practical route to uridine 5′-diphosphoglucuronic acid (UDP-GlcUA) from uridine 5′-diphosphoglucose (UDP-Glc) on a 1-g scale has been developed using uridine 5′-diphosphoglucose dehydrogenase (UDP-Glc DH, EC 1.1.1.22) from bovine liver. Crude UDP-Glc deh ... Full text Cite

Enzymes in organic synthesis 49. Resolutions of racemic monocyclic esters with pig liver esterase.

Journal Article Tetrahedron: Asymmetry · January 1, 1991 Pig liver esterase (PLE)- catalyzed hydrolyses of the racemic methyl esters of cyclobutane-, cyclohexane-, and cyclohex-4-ene-carboxylic acids bearing cis-2-methyl or cis-2-bromomethyl substituents are highly stereoselective, giving the corresponding acid ... Full text Cite

Enzymes in organic synthesis 50. Probing the dimensions of the large hydrophobic binding region of the active site of pig liver esterase using substituted aryl malonate substrates

Journal Article Tetrahedron: Asymmetry · January 1, 1991 The active site model reported recently for the synthetically useful enzyme pig liver esterase (PILE) permits the structural specificity and stereoselectivity of the enzyme to be interpreted and predicted for a wide range of substrates. The specifications ... Full text Cite

Molecular cloning of aldolases for synthetic applications.

Journal Article Annals of the New York Academy of Sciences · January 1990 Full text Cite

Active-Site Model for Interpreting and Predicting the Specificity of Pig Liver Esterase

Journal Article Journal of the American Chemical Society · January 1, 1990 Pig liver esterase (PLE) is one of the most useful enzymes for the preparation of valuable chiral synthons. However, its applications in asymmetric synthesis have been hampered by its seemingly unpredictable specificity. This disadvantage has now been over ... Full text Cite

Computer Software Reviews

Journal Article Journal of the American Chemical Society · March 1, 1989 Full text Cite

Enzyme-catalyzed synthesis of carbohydrates

Journal Article Tetrahedron · January 1, 1989 Full text Cite

Enzymes in organic synthesis. 42. Investigation of the effects of the isozymal composition of pig liver esterase on its stereoselectivity in preparative-scale ester hydrolyses of asymmetric synthetic value

Journal Article Journal of the American Chemical Society · January 1, 1988 The stereospecificities of the isozyme components of commercially available pig liver esterase have been shown to be essentially the same toward representative monocyclic and acyclic diester substrates. This removes previous concerns that the isozymal comp ... Full text Cite

Determination of the Absolute Configuration of Six-Membered-Ring Ketones by 13C NMR

Journal Article Journal of the American Chemical Society · March 1, 1987 The diastereotopic splitting of the 13C NMR signals of the (2R,3R)-2,3-butanediol acetals of 39 chiral six-membered-ring ketones, including 2- and 3-substituted cyclohexanones, 2-alkyltetrahydropyran-4-ones, and 2- and 3-alkyltetrahydrothiopyran- 4-ones, h ... Full text Cite

Preface

Journal Article Technovation · January 1, 1986 Full text Cite

Photolysis of some ortho-methylated monochlorobiphenyls

Journal Article Journal of the Chemical Society, Perkin Transactions 2 · January 1, 1983 A series of monochloro-o-methylated biphenyls was photolysed. Quantum yields of dechlorination lie in between the low values observed for 3- and 4-chlorobiphenyl and the high values obtained for 2-chlorobiphenyl. The results are interpreted in terms of rai ... Full text Cite

PHOTOCHEMISTRY OF BENZOPHENONE IN ACIDIFIED METHANOL

Journal Article JOURNAL OF CHEMICAL RESEARCH-S · January 1, 1983 Link to item Cite