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91.
《Electroanalysis》2005,17(20):1861-1864
Electrochemical study of barley grain lipid‐transfer protein (LTP) revealed that it may belong to the metal‐binding protein class. Using differential pulse polarography the presence of Cu(II) and Zn(II) ions in the native LTP structure was proved, as well as its affinity for binding Ni(II) ion. Application of a more sensitive electroanalytical technique, such as anodic stripping voltammetry with analyte preconcentration, revealed the presence of Pb(II) and Cd(II) ions and also enabled the following Hg(II) ion binding. Possible biological role of LTP in plant stress response and its contribution to barley phytoextraction potential are discussed. 相似文献
92.
Damien Thompson 《Chemphyschem》2007,8(11):1684-1693
Molecular recognition between guest ink molecules and beta-cyclodextrin (beta-CD) cavities at self-assembled monolayers provides a molecular printboard for nanopatterning applications. We recently used molecular dynamics (MD) simulations to describe the specificity of ink-printboard binding and here extend the simulations to include charged cyclodextrin hosts, necessary to broaden the chemistry of molecular printboards and bind charged inks such as the ferrocenium cation. Shifting to high pH, or alternatively grafting a charged sidearm onto beta-CD, created three distinct types of anionic beta-CD cavity and we used electronic structure calculations and MD simulations to measure host-guest charge transfer and binding strengths. We find that steric recognition of uncharged organic molecules is retained at the charged printboards, and that improved guest-host electrostatic contacts can strengthen binding of larger inks while penalising small inks, enhancing the level of discrimination. A prudent choice of complementary host-guest shape and charge states thus provides a means of tuning both ink binding strength and specificity at molecular printboards. 相似文献
93.
Brunsveld L Watzke A Durek T Alexandrov K Goody RS Waldmann H 《Chemistry (Weinheim an der Bergstrasse, Germany)》2005,11(9):2756-2772
Prenylated proteins with non-native functionalities are generally very difficult to obtain by recombinant or enzymatic means. The semisynthesis of preparative amounts of prenylated Rab guanosine triphosphatases (GTPases) from recombinant proteins and synthetic prenylated peptides depends largely on the availability of functionalised prenylated peptides corresponding to the proteins' native structure or modifications thereof. Here, we describe and compare solution-phase and solid-phase strategies for the generation of peptides corresponding to the prenylated C terminus of Rab7 GTPase. The solid-phase with utilisation of a hydrazide linker emerges as the more favourable approach. It allows a fast and practical synthesis of pure peptides and gives a high degree of flexibility in their modification. To facilitate the analysis of semisynthetic proteins, the synthesised peptides were equipped with a fluorescent group. Using the described approach, we introduced fluorophores at several different positions of the Rab7 C terminus. The position of the incorporated fluorescent groups in the peptides did not influence the protein-ligation reaction, as the generated peptides could be ligated onto thioester-tagged Rab7. However, it was found that the positioning of the fluorescent group had an influence on the functionality of the Rab7 proteins; analysis of the interaction of the semisynthetic Rab7 proteins with REP (Rab escort protein) and GDI (guanosine diphosphate dissociation inhibitor) molecules revealed that modification of the peptide side chains or of the C-terminal isoprenoid did not significantly interfere with complex formation. However, functionalisation of the C terminus was found to have an adverse effect on complex formation and stability, possibly reflecting low structural flexibility of the Rab GDI/REP molecules in the vicinity of the lipid-binding site. 相似文献
94.
本文综述了目前国际上对铁硫蛋白模型化合物研究的进展情况,介绍了NH---S氢键和芳香环在这些模型化合物及其天然蛋白中的作用。作为铁硫蛋白活性中心的模型,至今已有许多化合物被合成出来,通过这些模型化合物的研究知道,NH---S氢键和芳香环在调控配合物及天然蛋白的氧化还原电位和稳定性方面起着非常重要的作用。另外,作为顺式乌头酸酶、固氮酶等金属酶的模型,已成功地合成了含3Fe4S核以及含钼的铁硫簇合物。 相似文献
95.
Samuel K Yin W Stearns RA Tang YS Chaudhary AG Jewell JP Lanza T Lin LS Hagmann WK Evans DC Kumar S 《Journal of mass spectrometry : JMS》2003,38(2):211-221
Metabolic activation of drug candidates to electrophilic reactive metabolites that can covalently modify cellular macromolecules may result in acute and/or idiosyncratic immune system-mediated toxicities in humans. This presents a significant potential liability for the future development of these compounds as safe therapeutic agents. We present here an example of an approach where sites of metabolic activation within a new drug candidate series were rapidly identified using online liquid chromatography/multi-stage mass spectrometry on an ion trap mass spectrometer. This was accomplished by trapping the reactive intermediates formed upon incubation of compounds with rat and human liver microsomes as their corresponding glutathione conjugates and mass spectral characterization of these thiol adducts. Based on the structures of the GSH adducts identified, potential sites and mechanisms of bioactivation within the chemical structure were proposed. These metabolism studies were interfaced with iterative structural modifications of the chemical series in order to block these bioactivation sites within the molecule. This strategy led to a significant reduction in the propensity of the compounds to undergo metabolic activation as evidenced by reductions in the irreversible binding of radioactivity to liver microsomal material upon incubation of tritium-labeled compounds with this in vitro system. With the efficiency and throughput achievable with such an approach, it appears feasible to identify and address the metabolic activation potential of new drug leads during routine metabolite identification studies in an early drug discovery setting. 相似文献
96.
Elizabeth P.G. Arêas José A.G. Arêas James Hamburger Warner L. Peticolas Paulo S. Santos 《Journal of colloid and interface science》1996,180(2):578
A remarkably high viscosity has been induced in protein aqueous solutions by the addition of certain structurally related organic solvents. The effect has been observed for lysozyme aqueous solutions containing tetramethylurea (TMU), dimethylsulfoxide (DMSO), dimethylformamide, and hexamethylphosphortriamide. The effect has also been induced in ferrocytochrome c aqueous solutions by TMU. Critical concentrations for both the protein and organic solvent were verified for the onset of the viscosity increase. A common feature of the solvents which were able to induce the effect is a dipolar moiety (C=O, S → O and P → O) and a nonpolar region represented by the methyl groups. The resulting fluids show an extremely restricted flow and a typical non-Newtonian, pseudoplastic behavior. Use was made of1H nuclear magnetic resonance (NMR) and Raman spectroscopy to characterize protein structural modifications and of13C NMR to investigate changes in relaxation times and chemical shifts in the solvent/water solutions. A systematic rheological characterization of the systems was undertaken for some of the solvents, and unusual patterns of viscous effects were identified for the solvent/water systems both with and without protein. The process was found to be at least partially reversible, as concluded from the recovered original solution rheological characteristics and the original protein1H NMR spectrum, after eliminating the organic solvent by ultrafiltration. The whole process was characterized as consisting of two mutually independent stages. The first involves an extensive conformational transition of the polypeptide backbone, from a predominantly α-helical to increased random coiled and β-sheet structures, with the occurrence of nonorthodox protein secondary structures at regions above the solvent critical point. The second stage consists of short-lived interchain contacts leading to an entanglement of the macromolecular system as a whole. A microphase reversion in the organic solvent/water mixture, supported by13C NMR and rheological results, is proposed as the driving force causing the observed behavior. 相似文献
97.
The thermal properties of -lactoglobulin (-LG) were studied by differential scanning calorimetry (DSC) under different medium conditions.pH, neutral salts, protein perturbants, and polyols all affected the DSC characteristics of -LG. Acylation with fatty acids also changed the thermal properties, particularly peak width at half-height. The results suggest that the structural stability of -LG is controlled by non-covalent forces, particularly electrostatic and hydrophobic interactions. Disulfide bonds did not contribute to the thermal response of -LG. Fatty N-acyl-amino acids caused marked increases in thermal stability and decreases in denaturation enthalpy, and additional peaks were observed in the presence of some palmitoyl derivatives.Contribution No. 2310, Centre for Food and Animal Research.We thank D. Raymond for her excellent technical assistance. 相似文献
98.
Crommentuyn KM Rosing H Nan-Offeringa LG Hillebrand MJ Huitema AD Beijnen JH 《Journal of mass spectrometry : JMS》2003,38(2):157-166
HIV protease inhibitors are important antiretroviral drugs which have substantially reduced the morbidity and mortality associated with HIV-1 infection. Recent data have shown relationships between plasma concentrations of the protease inhibitors and clinical response, which makes therapeutic drug monitoring valuable. We have developed and validated an assay, using liquid chromatography coupled with electrospray tandem mass spectrometry (LC/MS/MS), for the routine quantification of the six licensed protease inhibitors (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir) and the pharmacologically active nelfinavir metabolite M8 in plasma. The sample pretreatment consisted of protein precipitation with a mixture of methanol and acetronitrile using only 100 microl of plasma. Chromatographic separation was performed on an Inertsil ODS3 column (50 x 2.0 mm i.d., particle size 5 microm), with a quick stepwise gradient using an acetate buffer (pH 5) and methanol, at a flow rate of 0.5 ml min(-1). The analytical run time was 5.5 min. The use of a 96-well plate autosampler allowed batch sizes up to 150 patient samples. The triple-quadrupole mass spectrometer was operated in the positive ion mode and multiple reaction monitoring was used for drug quantification. The method was validated over the concentration ranges 0.01-10 microg ml(-1) for indinavir and saquinavir, 0.1-10 microg ml(-1) for amprenavir, 0.05-10 microg ml(-1) for nelfinavir and ritonavir, 0.1-20 microg ml(-1) for lopinavir and 0.01-5 microg ml(-1) for M8. Saquinavir-d(5) and indinavir-d(6) were used as internal standards. The coefficients of variation were always <10% for both intra-day and inter-day precisions for each compound. Mean accuracies were also between the designated limits (+/-15%). The validated concentration ranges proved to be adequate in daily practice. This robust and fast LC/MS/MS assay is now successfully applied for routine therapeutic drug monitoring and pharmacokinetic studies in our hospital. 相似文献
99.
100.
Terenina M. B. Misharina T. A. Krikunova N. I. Golovnya R. V. 《Russian Chemical Bulletin》2001,50(6):1032-1036
Capillary gas chromatography was applied to study the sorption of aliphatic ketones (C6—C11), including metamers, from aqueous solutions by corn starch cryotextures. The amount of ketones sorbed by cryotextures depends linearly on their concentrations in the initial sol. Equations describing the concentration dependence of sorption were proposed. The shape of sorption isotherms reflects the strength of sorption. The binding constants and the number of binding sites were determined for weakly sorbed ketones. The length of alkyl substituent and the position of the functional group are the crucial factors governing the sorption of ketones under conditions of excess binding sites. It was found that the degree of sorption increases with an increase in the carbon chain length from 6 to 9 carbon atoms. The presence of cooperation of binding sites for ketone sorption by cryotextures was demonstrated. The major part of ketones is sorbed irreversibly. This fact points to the formation of supramolecular complexes. Ketones with lower molecular masses are better sorbed by cryotextures than by native starch grains. 相似文献