Covalent Bonds (covalent + bond)

Distribution by Scientific Domains
Distribution within Chemistry

Selected Abstracts

Film Growth and Surface Roughness with Effective Fluctuating Covalent Bonds in Evaporating Aqueous Solution of Reactive Hydrophobic and Polar Groups: A Computer Simulation Model

Shihai Yang
Abstract Summary: A computer simulation model is proposed to study film growth and surface roughness in aqueous (A) solution of hydrophobic (H) and hydrophilic (P) groups on a simple three dimensional lattice of size with an adsorbing substrate. Each group is represented by a particle with appropriate characteristics occupying a unit cube (i.e., eight sites). The Metropolis algorithm is used to move each particle stochastically. The aqueous constituents are allowed to evaporate while the concentration of H and P is constant. Reactions proceed from the substrate and bonded particles can hop within a fluctuating bond length. The film thickness () and its interface width () are examined for hardcore and interacting particles for a range of temperature (). Simulation data show a rapid increase in and followed by its non-monotonic growth and decay before reaching steady-state and near equilibrium () in asymptotic time step limit. The growth can be described by power laws, e.g., with a typical value of in initial time regime followed by at . For hardcore system, the equilibrium film thickness () and surface roughness () seem to scale linearly with the temperature, i.e., at low and at higher . For interacting functional groups in contrast, the long time (unsaturated) film thickness and surface roughness, and decay rapidly followed by a slow increase on raising the temperature. Growth of the average film thickness at a temperature . [source]

Early Structural Evolution of Native Cytochrome c after Solvent Removal

CHEMBIOCHEM, Issue 15 2008
Michal Z. Steinberg
Abstract Electrospray ionization transfers thermally labile biomolecules, such as proteins, from solution into the gas phase, where they can be studied by mass spectrometry. Covalent bonds are generally preserved during and after the phase transition, but it is less clear to what extent noncovalent interactions are affected by the new gaseous environment. Here, we present atomic-level computational data on the structural rearrangement of native cytochrome c immediately after solvent removal. The first structural changes after desolvation occur surprisingly early, on a timescale of picoseconds. For the time segment of up to 4.2 ns investigated here, we observed no significant breaking of native noncovalent bonds; instead, we found formation of new noncovalent bonds. This generally involves charged residues on the protein surface, resulting in transiently stabilized intermediate structures with a global fold that is essentially the same as that in solution. Comparison with data from native electron capture dissociation experiments corroborates both its mechanistic postulations and our computational predictions, and suggests that global structural changes take place on a millisecond timescale not covered by our simulations. [source]

Rapid capillary electrophoresis time-of-flight mass spectrometry separations of peptides and proteins using a monoquaternarized piperazine compound (M7C4I) for capillary coatings

Anisa Elhamili
Abstract A monoquaternarized piperazine, 1-(4-iodobutyl) 4-aza-1-azoniabicyclo[2,2,2] octane iodide (M7C4I), has been evaluated as a surface derivatization reagent for CE in combination with TOF MS for the analysis of proteins, peptides, and protein digests. The M7C4I piperazine, at alkaline pH, forms a covalent bond via alkylation of the ionized silanols producing a cationic surface with a highly stable and reversed EOF. The obtained surface yields rapid separations (less than 5,min) of peptides and proteins at acidic pH with high separation efficiencies (up to 1.1106 plates/m for peptides and up to 1.8106 plates/m for proteins) and no observed bleeding of the coating reagent into the mass spectrometer. The simplicity of the coating procedure also enables fast (2,min) regeneration of the surface, if necessary. This is useful in the analysis of complex samples in order to prevent possible memory effects. The potential of using M7C4I-coated capillaries for MS analysis of complex samples is demonstrated by the separation of peptides, proteins, and protein digests. Even more, the spectacular thing in which large intact proteins with molecular masses over 0.5,MDa could be separated. The coating showed good ability to handle these large proteins with high efficiency and retained peak shape as demonstrated by separation of IgG1 (150,kDa) and thyroglobulin (669,kDa). [source]

Ruthenium-to-Platinum Interactions in ,6,,1 NCN-Pincer Arene Heterobimetallic Complexes: An Experimental and Theoretical Study

Sylvestre Bonnet
Abstract A series of ,6,,1 -heterobimetallic complexes have been prepared in which a [Ru(,6 -arene)(C5R5)]+ fragment (R = H or Me) and an ,1 -NCN-pincer platinum fragment are combined within the same molecule. In complexes [2]+ and [3]+, the ruthenium and platinum centers are ,6 and ,1 coordinated, respectively, to the same arene ring, whereas in [4A]+ and [5A]+ they are coordinated to two different arene rings that are linked with a covalent bond ([4A]+) or an ethyl bridge ([5A]+). Upon changing the organic manifold between both metal centers, very strong ([2]+) to very weak ([5A]+) ruthenium-to-platinum interactions are obtained. Experimentally, X-ray crystal structures show an increaing steric hindrance when the Ru,Pt distance diminishes, and electrochemical and 195Pt NMR spectroscopic studies show a decreasing electron density on platinum from [5A]+ to [2]+. Theoretical DFT calculations were undertaken, which show an increasing charge on platinum from [5A]+ to [2]+. Our theoretical analysis shows that the particularly strong ruthenium-to-platinum electronic interactions in [2]+ and [3]+ do not come from binding of ruthenium to platinum, but from the pincer Cipso sharing its electron density between both metal centers, which decreases the , donation to platinum, and from increased backdonation of the platinum d electrons into the , system of the arene ring. [source]

Synthesis of New Thiophene-Substituted 3,3-Diphenyl-3H -naphtho[2,1- b]pyrans by Cross-Coupling Reactions, Precursors of Photomodulated Materials

Michel Frigoli
Abstract 3,3-Diphenyl-3H -naphtho[2,1- b]pyrans linked to one, two, or three thiophene nuclei in different positions of the naphthalene moiety (5, 6, 8, and 9) by a covalent bond have been prepared in good yields. A Suzuki cross-coupling reaction was used with two possible strategies: chromenization before the coupling with oligothiophenes or chromenization after the coupling, the main intermediates being the diphenyl propargylic alcohol, the functionalized naphthol derivatives, and the thiophenic boronates. The overall yields for obtaining such photochromic compounds are generally quite satisfying. For the 7-position, the coupling reaction has been realized using a Grignard reaction between a tetralone derivative and a thiophenic bromo magnesium intermediate. ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source]

Covalently crosslinked complexes of bovine adrenodoxin with adrenodoxin reductase and cytochrome P450scc

FEBS JOURNAL, Issue 6 2001
Edman degradation of complexes of the steroidogenic hydroxylase system, Mass spectrometry
NADPH-dependent adrenodoxin reductase, adrenodoxin and several diverse cytochromes P450 constitute the mitochondrial steroid hydroxylase system of vertebrates. During the reaction cycle, adrenodoxin transfers electrons from the FAD of adrenodoxin reductase to the heme iron of the catalytically active cytochrome P450 (P450scc). A shuttle model for adrenodoxin or an organized cluster model of all three components has been discussed to explain electron transfer from adrenodoxin reductase to P450. Here, we characterize new covalent, zero-length crosslinks mediated by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide between bovine adrenodoxin and adrenodoxin reductase, and between adrenodoxin and P450scc, respectively, which allow to discriminate between the electron transfer models. Using Edman degradation, mass spectrometry and X-ray crystallography a crosslink between adrenodoxin reductase Lys27 and adrenodoxin Asp39 was detected, establishing a secondary polar interaction site between both molecules. No crosslink exists in the primary polar interaction site around the acidic residues Asp76 to Asp79 of adrenodoxin. However, in a covalent complex of adrenodoxin and P450scc, adrenodoxin Asp79 is involved in a crosslink to Lys403 of P450scc. No steroidogenic hydroxylase activity could be detected in an adrenodoxin ,P450scc complex/adrenodoxin reductase test system. Because the acidic residues Asp76 and Asp79 belong to the binding site of adrenodoxin to adrenodoxin reductase, as well as to the P450scc, the covalent bond within the adrenodoxin,P450scc complex prevents electron transfer by a putative shuttle mechanism. Thus, chemical crosslinking provides evidence favoring the shuttle model over the cluster model for the steroid hydroxylase system. [source]

Inhibition of Diamino Pelargonic Acid Aminotransferase, an Enzyme of the Biotin Biosynthetic Pathway, by Amiclenomycin: A Mechanistic Study

Stphane Mann
The mechanism of action of amiclenomycin (1a), a naturally occuring inhibitor of diaminopelargonic acid aminotransferase, has been established. The enzyme catalyzes the formation of an aromatic adduct between the inhibitor and pyridoxal-5,-phosphate. The structure of the adduct, determined by mass spectrometry, is in agreement with the reported X-ray crystal structure. Kinetic parameters, characteristic of kcat inhibitors, have been observed, with a KI value of 2,,M and a kinact value of 0.4,min,1. The irreversibility of the inactivation observed, in spite of the absence of covalent bond between the inhibitor and the protein, reveals the high affinity of the adduct for the active site. Two other cis -1-amino-4-substituted-cyclohexa-2,5-dienes, 3a and 4a, were also found to efficiently inhibit the enzyme. The trans -isomers were either much less potent (1b) or inactive (3b and 4b). The aminocyclohexadiene moiety, which is, apparently, responsible for the inhibition, could constitute an original pharmacophore for the design of new herbicides. [source]

Histidine and not tyrosine is required for the Peroxide-induced formation of haem to protein cross-linked myoglobin

IUBMB LIFE, Issue 8-9 2007
Brandon J. Reeder
Abstract Peroxide-induced oxidative modifications of haem proteins such as myoglobin and haemoglobin can lead to the formation of a covalent bond between the haem and globin. These haem to protein cross-linked forms of myoglobin and haemoglobin are cytotoxic and have been identified in pathological conditions in vivo. An understanding of the mechanism of haem to protein cross-link formation could provide important information on the mechanisms of the oxidative processes that lead to pathological complications associated with the formation of these altered myoglobins and haemoglobins. We have re-examined the mechanism of the formation of haem to protein cross-link to test the previously reported hypothesis that the haem forms a covalent bond to the protein via the tyrosine 103 residue (Catalano, C. E., Choe, Y. S., Ortiz de Montellano, P. R., J. Biol. Chem. 1989, 10534 - 10541). Comparison of native horse myoglobin, recombinant sperm whale myoglobin and Tyr103 , Phe sperm whale mutant shows that, contrary to the previously proposed mechanism of haem to protein cross-link formation, the absence of tyrosine 103 has no impact on the formation of haem to protein cross-links. In contrast, we have found that engineered myoglobins that lack the distal histidine residue either cannot generate haem to protein cross-links or show greatly suppressed levels of modified protein. Moreover, addition of a distal histidine to myoglobin from Aplysia limacina, that naturally lacks this histidine, restores the haem protein's capacity to generate haem to protein cross-links. The distal histidine is, therefore, vital for the formation of haem to protein cross-link and we explore this outcome. [source]

Flocculated decolorization of vinylsulfone reactive dye solutions with a ,-cyclodextrin-based copolymer

Xiuzhi Tian
Abstract A ,-cyclodextrin (,-CD)-based copolymer (,-CD,maleic anhydride,N -trimethylaminoethylmethacrylate chloride) with good thermal stability was designed and synthesized for flocculated decolorization of Reactive Brilliant Blue KN-R solutions. Jar tests indicated that with the optimal stirring mode as 120 rpm for 5 min and then 40 rpm for 5 min with a flocculant-to-dye ratio of 2 : 5 (w/w), a pH of 8,10, and a temperature of 20C, the maximum color removal reached. It is reported first in this article that, in addition to the polymer bridge and charge neutralization, the covalent bond of the reactive dye to the target flocculant molecules, which had a similar chemical structure to that of cellulose, contributed to the mechanism of flocculated decolorization. 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010 [source]

Effect of the structure of silane-coupling agent on dynamic mechanical properties of dental resin-nanocomposites

Irini D. Sideridou
Abstract This work was aimed at the study by dynamic mechanical analysis (DMA) of dental composites consisted of a Bis-GMA/TEGDMA (50/50 wt/wt) matrix and silica nanoparticles (Aerosil OX50) as filler, silanized with various silanes. The silanes used were 3-[(1,3(2)-dimethacryloyloxypropyl)-2 (3)-oxycarbonylamido] propyltriethoxy-silane (UDMS), 3-methacryloxypropyl-trimethoxysilane (MPS), octyltrimethoxysilane (OTMS), blends of UDMS/OTMS (50/50 wt/wt), or MPS/OTMS (50/50 wt/wt). The total amount of silane was kept constant at 10% by weight fraction relative to the filler weight. The silanized nanoparticles were mixed with the dimethacrylate matrix (60% filler by weight fraction). The composites were light cured and tested by DMA for the determination of storage modulus (E,), loss modulus (E,), tangent delta (tan ,), and glass transition temperature (Tg). Measurements were performed in samples immediately after curing and samples stored in water at 37C for 1, 7, 30, or 120 days. OTMS-composite in which OTMS does not form covalent bond with the dimethacrylate matrix showed lower elastic modulus both in dry and wet conditions. The ability of bifunctional UDMS for crosslinking was found not to increase the elastic behavior of the composite, as it was expected, compared with that of MPS-composite, because of the high amount of the silane used. After immersion in water the elastic modulus of OTMS-composite remained constant, while that of the other composites increased after 1 day and then remained constant up to 120 days. 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008 [source]

Dichlorvos, chlorpyrifos oxon and Aldicarb adducts of butyrylcholinesterase, detected by mass spectrometry in human plasma following deliberate overdose

Bin Li
Abstract The goal of this study was to develop a method to detect pesticide adducts in tryptic digests of butyrylcholinesterase in human plasma from patients poisoned by pesticides. Adducts to butyrylcholinesterase in human serum may serve as biomarkers of pesticide exposure because organophosphorus and carbamate pesticides make a covalent bond with the active site serine of butyrylcholinesterase. Serum samples from five attempted suicides (with dichlorvos, Aldicarb, Baygon and an unknown pesticide) and from one patient who accidentally inhaled dichlorvos were analyzed. Butyrylcholinesterase was purified from 2 ml serum by ion exchange chromatography at pH 4, followed by procainamide affinity chromatography at pH 7. The purified butyrylcholinesterase was denatured, digested with trypsin and the modified peptide isolated by HPLC. The purified peptide was analyzed by multiple reaction monitoring in a QTRAP 4000 mass spectrometer. This method successfully identified the pesticide-adducted butyrylcholinesterase peptide in four patients whose butyrylcholinesterase was inhibited 60,84%, but not in two patients whose inhibition levels were 8 and 22%. It is expected that low inhibition levels will require analysis of larger serum plasma volumes. In conclusion, a mass spectrometry method for identification of exposure to live toxic pesticides has been developed, based on identification of pesticide adducts on the active site serine of human butyrylcholinesterase. Copyright 2010 John Wiley & Sons, Ltd. [source]

Phototropins and Their LOV Domains: Versatile Plant Blue-Light Receptors

Winslow R. Briggs
Abstract The phototropins phot1 and phot2 are plant blue-light receptors that mediate phototropism, chloroplast movements, stomatal opening, leaf expansion, the rapid inhibition of hypocotyl growth in etiolated seedlings, and possibly solar tracking by leaves in those species in which it occurs. The phototropins are plasma membrane-associated hydrophilic proteins with two chromophore domains (designated LOV1 and LOV2 for their resemblance to domains in other signaling proteins that detect light, oxygen, or voltage) in their N-terminal half and a classic serine/threonine kinase domain in their C-terminal half. Both chromophore domains bind flavin mononucleotide (FMN) and both undergo light-activated formation of a covalent bond between a nearby cysteine and the C(4a) carbon of the FMN to form the signaling state. LOV2-cysteinyl adduct formation leads to the release downstream of a tightly bound amphipathic ,-helix, a step required for activation of the kinase function. This cysteinyl adduct then slowly decays over a matter of seconds or minutes to return the photoreceptor chromophore modules to their ground state. Functional LOV2 is required for light-activated phosphorylation and for various blue-light responses mediated by the phototropins. The function of LOV1 is still unknown, although it may serve to modulate the signal generated by LOV2. The LOV domain is an ancient chromophore module found in a wide range of otherwise unrelated proteins in fungi and prokaryotes, the latter including cyanobacteria, eubacteria, and archaea. Further general reviews on the phototropins are those by Celaya and Liscum (2005) and Christie and Briggs (2005). [source]

Amphiphilic polymer conetworks prepared by controlled radical polymerization using a nitroxide cross-linker

Weijie Zhao
Abstract Tandem atom transfer radical polymerization (ATRP) and nitroxide-mediated radical polymerization (NMRP) were used to synthesize a polystyrene- co -poly(acrylic acid) (poly(St- co -AA)) network, in which the two components were interconnected by covalent bond. First, a specific cross-linker, 1,4-bis(1,-(4,-acryloyloxy-2,,2,,6,,6,-tetramethylpiperidinyloxy)ethyl)benzene (di -AET), a bifunctional alkoxyamine possessing two acrylate groups, was copolymerized with tert -butyl acrylate through ATRP to prepare a precursor gel. The gel was then used to initiate the NMRP of styrene to prepare poly(St- co -(t -BA)) conetwork, in which the cross-linkages are composed of polystyrene segments. Finally, the poly(St- co -(t -BA)) conetwork was hydrolyzed to produce amphiphilic poly(St- co -AA) conetwork. The resulting gels show swelling ability in both organic solvent and water, which is characteristic of amphiphilic conetworks. 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 4141,4149, 2010 [source]

Poly(vinyltriethoxysilane) modified MWCNT/polyimide nanocomposites,Preparation, morphological, mechanical, and electrical properties

Siu-Ming Yuen
Abstract Multi-walled carbon nanotube (MWCNT) modified by vinyltriethoxysilane (VTES) via free radical reaction has been prepared (poly (vinyltriethoxysilane) modified MWCNTs, PVTES-MWCNT). Precursor of polyimide, polyamic acid has been synthesized by reacting 4,4,-oxydianiline with 3,3,,4,4,-benzophenone tetracarboxylic dianhydride. PVTES-MWCNT were then mixed with polyamic acid and heated to 300 C to form CNT/polyimide composite. During the imidization processes, the silanes on CNT surface reacted with each other and may be connected together by covalent bond (SiOSi). The PVTES-MWCNT was analyzed by Fourier transform infrared and X-ray photoelectron spectroscopy. The PVTES-MWCNT/polyimide composites were analyzed by CP/MAS solid state 29Si nuclear magnetic resonance (NMR) spectroscopy. Morphological properties of the PVTES-MWCNT/polyimide composites were investigated by scanning electron microscope and transmission electron microscope. Electrical conductivity increased dramatically comparing to the unmodified MWCNT/polyimide composites. Mechanical properties of nanocomposite were enhanced significantly by PVTES-MWCNT. 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 803,816, 2008 [source]

Chromophore Interaction in Xanthorhodopsin,Retinal Dependence of Salinixanthin Binding,

Eleonora S. Imasheva
Xanthorhodopsin is a light-driven proton pump in the extremely halophilic bacterium Salinibacter ruber. Its unique feature is that besides retinal it has a carotenoid, salinixanthin, with a light harvesting function. Tight and specific binding of the carotenoid antenna is controlled by binding of the retinal. Addition of all- trans retinal to xanthorhodopsin bleached with hydroxylamine restores not only the retinal chromophore absorption band, but causes sharpening of the salinixanthin bands reflecting its rigid binding by the protein. In this report we examine the correlation of the changes in the two chromophores during bleaching and reconstitution with native all- trans retinal, artificial retinal analogs and retinol. Bleaching and reconstitution both appear to be multistage processes. The carotenoid absorption changes during bleaching occurred not only upon hydrolysis of the Schiff base but continued while the retinal was leaving its binding site. In the case of reconstitution, the 13-desmethyl analog formed the protonated Schiff base slower than retinal, and provided the opportunity to observe changes in carotenoid binding at various stages. The characteristic sharpening of the carotenoid bands, indicative of its reduced conformational heterogeneity in the binding site, occurs when the retinal occupies the binding site but the covalent bond to Lys-240 via a Schiff base is not yet formed. This is confirmed by the results for retinol reconstitution, where the Schiff base does not form but the carotenoid exhibits its characteristic spectral change from the binding. [source]

Role of interfaces on the direct tunneling and the inelastic tunneling behaviors through metal/alkylsilane/silicon junctions

D. K. Aswal
Abstract We studied the influence of the end group of the alkylsilane molecule used in Self Assembled Monolayer (SAM) in Silicon/SAM/Metal junctions. By Inelastic Electron Tunneling spectroscopy (IETS), we showed the formation of a covalent bond between the molecules and the gold electrode in the case of a thiol terminated alkylsilane. By electrical characterizations, we demonstrated that the thiol group at the interface avoids diffusion of gold into the molecule even for a 3 carbons chain. For this short molecule, we observed pure tunnel conduction with barrier height at the monolayer/Si and monolayer/Au interfaces found to be respectively 2.14 and 2.56 eV. These values were obtained using Simmons equation with an effective mass parameter m * = 0.16me (me = mass of the electron). This extends the demonstration of the excellent tunnel dielectric behavior of these organic monolayers down to 3 carbon atoms with a thiol/Au bond at the interface. ( 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source]

Peculiarities of soliton motion in molecular systems with high dispersion

V. V. Krasilnikov
Abstract In this work, features of propagating protons along molecular chain of hydrogen bonds are described from position of soliton dynamics with taking into account interaction of first and second neighbors of a proton sublattice. It is proposed extension of the model that is an endless chain of water molecules in which formation of hydrogen bonds is due to participating one proton of every water molecule, a second proton no participating in hydrogen bond and being confined by covalent bond of an oxygen atom. Nonlinearity is due to peculiar properties of proton sublattice potential. The model used to obtain continual equations which contain the spatial derivatives of the fourth order that is related with dispersion of longwave oscillations. The availability of such a dispersion changes essentially dynamics of the molecular chain, which allows of manifesting new peculiarities of propagating nonlinear excitations. It is shown there are two new sorts of charge density excitations transferred by solitons determined as exact analytic dependences in such a system. ( 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source]

C4d Deposition and Clearance in Cardiac Transplants Correlates With Alloantibody Levels and Rejection in Rats

K. Minami
Antibody-mediated rejection of human cardiac transplants is correlated with C4d deposits and macrophage infiltrates in capillaries of endomyocardial biopsies. We produced an antibody to rat C4d to study C4d deposition and clearance in Lewis rats that were sensitized with a blood transfusion from DA rats 7, 14 or 21 days before cardiac transplantation. Cyclosporin A (CsA) immunosuppression was initiated after transplantation at a dose that inhibited graft rejection, antibody production and C4d deposition in unsensitized recipients. Blood transfusion elicited high levels of circulating IgG alloantibodies, predominantly of the complement-activating IgG2b subclass, that peaked 14 days after transplantation. At this time, macrophages accumulated in capillaries, and C4d deposits were diffuse and intense on arteries, capillaries and veins. Grafts that survived 90 days in sensitized recipients still had deposits of C4d that were associated with increased interstitial fibrosis and vasculopathy in arteries. Clearance of C4d was determined by retransplanting DA cardiac allografts from Lewis recipients back to DA recipients. C4d deposits were decreased to minimal levels within 5 days after retransplantation. Thus, C4d deposition is not limited to the capillaries, but extends throughout the arterial tree, and despite formation of a covalent bond, C4d is cleared within days. [source]

Bis[4-(trimethylammonio)phenyl] disulfide diiodide acetone solvate

Zheng Zhang
The title compound, C18H26N2S22+2I,2C3H6O, is an intermediate in the design of the zwitterionic thiolate 4-(trimethylammonio)benzenethiolate (Tab), in which a pair of aryl-substituted S atoms are linked by a covalent bond. The central S,S bond length is 2.020,(3), and the Car,S,S,Car torsion angle is ,84.1,(2). The crystal structure is stabilized by nonclassical hydrogen bonds which occur as intramolecular C,H...I interactions and intermolecular C,H...S and C,H...O contacts. In the crystal structure, both the dication and the two symmetrically independent iodide counter-anions are located on twofold crystallographic axes, whereas the acetone solvent molecule occupies a general position. [source]

Structure of full-length ubiquitin-conjugating enzyme E2-25K (huntingtin-interacting protein 2)

Randall C. Wilson
The ubiquitin-conjugating enzyme E2-25K has been identified as a huntingtin (the key protein in Huntington's disease) interacting protein and has been shown to play a role in mediating the toxicity of A,, the principal protein involved in Alzheimer's disease pathogenesis. E2-25K is a dual-domain protein with an ubiquitin-associated (UBA) domain as well as a conserved ubiquitin-conjugating (UBC) domain which catalyzes the formation of a covalent bond between the C-terminal glycine of an ubiquitin molecule and the ,-amine of a lysine residue on the acceptor protein as part of the ubiquitin-proteasome pathway. The crystal structures of E2-25K M172A mutant protein at pH 6.5 and pH 8.5 were determined to 1.9 and 2.2, resolution, respectively. Examination of the structures revealed domain,domain interactions between the UBC and UBA domains which have not previously been reported. [source]

SUMOylation and cell signalling

Artemisia M. Andreou
Abstract SUMOylation is a highly transient post-translational protein modification. Attachment of SUMO to target proteins occurs via a number of specific activating and ligating enzymes that form the SUMO-substrate complex, and other SUMO-specific proteases that cleave the covalent bond, thus leaving both SUMO and target protein free for the next round of modification. SUMO modification has major effects on numerous aspects of substrate function, including subcellular localisation, regulation of their target genes, and interactions with other molecules. The modified SUMO-protein complex is a very transient state, and it thus facilitates rapid response and actions by the cell, when needed. Like phosphorylation, acetylation and ubiquitination, SUMOylation has been associated with a number of cellular processes. In addition to its nuclear role, important sides of mitochondrial activity, stress response signalling and the decision of cells to undergo senescence or apoptosis, have now been shown to involve the SUMO pathway. With ever increasing numbers of reports linking SUMO to human disease, like neurodegeneration and cancer metastasis, it is highly likely that novel and equally important functions of components of the SUMOylation process in cell signalling pathways will be elucidated in the near future. [source]

How to Produce a Chemical Defense: Structural Elucidation and Anatomical Distribution of Aplysioviolin and Phycoerythrobilin in the Sea Hare Aplysia californica

Michiya Kamio
Abstract We previously used bioassay-guided fractionation to identify phycoerythrobilin (1) and its monomethyl ester, aplysioviolin (2), as components in the ink secretion of a marine gastropod, the sea hare Aplysia californica, that act as chemical deterrents against predatory blue crabs. This was the first report of 1 as a natural product. Compound 2 was previously reported as a natural product from three species of Aplysia (A. fasciata, A. dactylomela, and A. parvula), but the reported structure and composition of stereoisomers of 2 are different among these species. Sea hares are thought to produce 2 from phycoerythrin, a photosynthetic pigment in their red-algal diet composed of a phycobiliprotein covalently linked to the chromophore 1, by cleavage of the covalent bond and methylation of 1, but neither the sequence nor the anatomical location of the cleavage and methylation is known. In this study, we clarify the structure of 1 and 2 in ink secretion of A. californica, and describe the distribution of 1 and 2 in the tissues of sea hares. We conclude that cleavage of the covalent bond in phycoerythrin occurs first, forming 1 in the digestive gland, followed by methylation of 1 to yield 2 in the ink gland. [source]

Mechanistic Study of the Reaction of Thiol-Containing Enzymes with ,,,-Unsaturated Carbonyl Substrates by Computation and Chemoassays

CHEMMEDCHEM, Issue 6 2010
Alexander Paasche
Abstract We investigated the reactions between substituted ,,,-unsaturated carbonyl compounds (Michael systems) and thiols by computations as well as chemoassays. The results give insight into variations in the underlying mechanisms as a function of the substitution pattern. This is of interest for the mechanisms of inhibition of the SARS coronavirus main protease (SARS-CoV Mpro) by etacrynic acid derivatives as well as for the excess toxicity of substituted ,,,-unsaturated carbonyl compounds. This study compares possible reaction courses including 1,4-addition followed by a ketonization step, and underscores the importance of a base-catalyzed step for the reactivity of thiol groups in enzymes. Phenyl and methyl substituents at the Michael system decrease the reactivity of the electrophilic compound, but chlorophenyl substituents partly recover the reactivity. Computations also indicate that electron-pushing substituents lead to a change in the reaction mechanism. The conformation of the Michael system is also found to significantly influence reactivity: the s - cis conformation leads to higher reactivity than the s - trans conformation. The computed data explain the trends in measured inhibition potencies of substituted ,,,-unsaturated carbonyl compounds and of reaction rates in chemical assays. They also indicate that the reversibility of inhibition does not stand in contrast to the formation of a new covalent bond between inhibitor and protease. [source]

Discrimination of enantiomers of ,-amino acids by chiral derivatizing reagents from trans -1,2-diaminocyclohexane,

CHIRALITY, Issue 3-4 2008
Magdalena Kaik
Abstract New chiral derivatizing reagents (CDAs) derived from trans -1,2-diaminocyclohexane, having an electron-deficient aromatic substituent (either an aromatic imide or 3,5-dinitrobenzamide) and rigid structure (either an amide or a urea linker), are reported. Significant shift differences of diastereotopic protons in the 1H NMR signals are observed for enantiomers of suitably protected ,-amino acids, linked to CDA by a covalent bond. A simple, general model rationalizing the observed enantiomer discrimination and based on semiempirical conformational search is presented. Chirality, 2008. 2007 Wiley-Liss, Inc. [source]

Study of Factors Affecting Molecular Behaviors in Phenothiazine-Mediated Biosensing by Electrochemical and Spectroscopic Methods

Abstract Reagentless glucose-detecting biosensors were constructed by incorporating a series of phenothiazine derivatives as mediators onto chitosan (CHIT) matrix via different covalent bonds, wherein glucose oxidase (GOx) was employed as the enzyme. Electrochemical studies show significant decrease in the electrocatalytic current during cyclic voltammetric and amperometric measurements, resulting from complexes formation between GOx and phenothiazine molecules. This behavior was further verified by spectroscopic studies. The decrease in the peak intensity at 258,nm is due to the gradual complexes formation over time, consistent to the decrease in the current signal in electrochemical investigations. Correlation with the molecular structures of phenothiazine derivatives reveals a strong relationship between the hydrophobicity of the mediators and the stability of the biosensor electrodes. [source]

Redox Active Two-Component Films of Palladium and Covalently Linked Zinc Porphyrin,Fullerene Dyad

Marta Plonska
Abstract Redox active films have been generated electrochemically by the reduction of dyads consisting of fullerene C60 covalently linked to zinc meso -tetraphenyloporphyrin, ZnPC60, and palladium acetate. The films are believed to consist of a polymeric network formed via covalent bonds between the palladium atoms and the fullerene moieties. In these films, the zinc porphyrin moiety is covalently linked to the polymeric chains through the pyrrolidine ring of the fullerene. The ZnPC60/Pt films are electrochemically active in both positive and negative potential excursions. At positive potentials, two oxidation steps for the zinc porphyrin are observed. In the negative potential range, electron transfer processes involving the zinc porphyrin and the fullerene entities are observed. Film formation is also accompanied by palladium deposition on the electrode surface. The presence of a metallic phase in the film influences its morphology, structure and electrochemical properties. [source]

Asymmmetric Diamino Functionalization of Nanotubes Assisted by BOC Protection and Their Epoxy Nanocomposites

Yao Zhao
Abstract Homogenous dispersion and strong interfacial bonding are prerequisites for taking full advantage of the mechanical properties of nanotubes in a composite. In order to simultaneously achieve both conditions, a highly efficient and mechanically non-destructive functionalization of nanotubes is developed. With fluoronanotubes as the precursor, asymmetric diamine molecules, N -BOC-1,6-diaminohexane, are used to replace fluorines on the wall of fluoronanotubes and construct covalent bonding to the surface of the nanotubes. A BOC de-protection reaction is conducted and the resulting exposed amino groups create strong covalent bonds with the matrix in the course of epoxy ring-opening etherification and curing chemical reactions. In comparison with the conventional functionalization based on symmetric diamine molecules, the functionalized nanotubes derived from the BOC-protected diamine molecule are more dispersed within the epoxy matrix. Dynamic mechanical analysis shows that the functionalized nanotubes have better crosslinking with the matrix. The composites reinforced by the nanotubes demonstrate improvement in various mechanical properties. The Young's Modulus, ultimate tensile strength, and storage modulus of composites loaded with 0.5 wt% functionalized nanotubes are enhanced by 30%, 25%, and 10%, respectively, compared with the neat epoxy. The increase of the glass transition temperature, as much as 10 C, makes the composites suited for engineering applications under higher temperatures. The new functionalization method allows for an competitive enhancement in the composite performance in use of relatively low cost raw nanotubes at a small loading level. The reinforcement mechanism of the functionalized nanotubes in the epoxy resin is discussed. [source]

Synthesis of Components for the Generation of Constitutional Dynamic Analogues of Nucleic Acids

Abstract The introduction of dynamic covalent polymers, in which the monomer units are linked by reversible covalent bonds and can undergo component exchange, opens up new possibilities for the generation of functional materials. Extending this approach to the generation of dynamic biopolymers in aqueous media, which are able to adapt constitution (sequence, length) to external factors (e.g., environment, medium, template), would provide an alternative approach to the de novo design of functional dynamic bio-macromolecules. As a first step towards this goal, various mono- and bifunctionalised (hetero- and homotopic) nucleic acid-derived building blocks of type I,X have been synthesised for the generation of dynamic main-chain and side-chain reversible nucleic acid analogues. Hydrazide- and/or acetal (protected carbonyl)-functionalised components were selected, which differ in terms of flexibility, length, net formal charge, and hydrazide/acetal substituents, in order to explore how such factors may affect the properties (structure, solubility, molecular recognition features) of the polymer products that may be generated by polycondensation. [source]

Progress with Molecular Electronic Junctions: Meeting Experimental Challenges in Design and Fabrication

Richard L. McCreery
Abstract Molecular electronics seeks to incorporate molecular components as functional elements in electronic devices. There are numerous strategies reported to date for the fabrication, design, and characterization of such devices, but a broadly accepted example showing structure-dependent conductance behavior has not yet emerged. This progress report focuses on experimental methods for making both single-molecule and ensemble molecular junctions, and highlights key results from these efforts. Based on some general objectives of the field, particular experiments are presented to show progress in several important areas, and also to define those areas that still need attention. Some of the variable behavior of ostensibly similar junctions reported in the literature is attributable to differences in the way the junctions are fabricated. These differences are due, in part, to the multitude of methods for supporting the molecular layer on the substrate, including methods that utilize physical adsorption and covalent bonds, and to the numerous strategies for making top contacts. After discussing recent experimental progress in molecular electronics, an assessment of the current state of the field is presented, along with a proposed road map that can be used to assess progress in the future. [source]

Atomic-orbital-symmetry based ,-, ,-, and ,-decomposition analysis of bond orders

Olga V. Sizova
Abstract The atomic-orbital-symmetry based (AOSB) scheme for the decomposition of Mayer and Wiberg bond orders into ,-, ,-, and ,-components is used to investigate different types of covalent bonds. Four series of compounds are studied: simple molecules with homonuclear bonds, inorganic molecules with polar heteronuclear bonds, [Ru(CN)5(XY)]q transition metal complexes with ,-acceptor ligands, and dimetal complexes with multiple metal,metal bonds. 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2009 [source]