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81.
Dagnino-Subiabre A Cassels BK Baez S Johansson AS Mannervik B Segura-Aguilar J 《Biochemical and biophysical research communications》2000,274(1):32-36
Human glutathione transferase M2-2 prevents the formation of neurotoxic aminochrome and dopachrome by catalyzing the conjugation of dopamine and dopa o-quinone with glutathione. NMR analysis of dopamine and dopa o-quinone-glutathione conjugates revealed that the addition of glutathione was at C-5 to form 5-S-glutathionyl-dopamine and 5-S-glutathionyl-dopa, respectively. Both conjugates were found to be resistant to oxidation by biological oxidizing agents such as O(2), H(2)O(2), and O(*-)(2), and the glutathione transferase-catalyzed reaction can therefore serve a neuroprotective antioxidant function. 相似文献
82.
Isolation of a coaggregation-inhibiting cell wall polysaccharide from Streptococcus sanguis H1. 总被引:6,自引:2,他引:4 下载免费PDF全文
Coaggregation between Streptococcus sanguis H1 and Capnocytophaga ochracea ATCC 33596 cells is mediated by a carbohydrate receptor on the former and an adhesin on the latter. Two methods were used to release the carbohydrate receptor from the gram-positive streptococcus, autoclaving and mutanolysin treatment. The polysaccharide released from the streptococcal cell wall by either treatment was purified by ion-exchange chromatography; this polysaccharide inhibited coaggregation when preincubated with the gram-negative capnocytophaga partner. After hydrolysis of the polysaccharide by hydrofluoric acid (HF), the major oligosaccharide of the polysaccharide was purified by high-performance liquid chromatography. By analysis of the HF hydrolysis of the polysaccharide and the purified oligosaccharide, this major oligosaccharide appeared to be the repeating unit of the polysaccharide, with minor components resulting from internal hydrolysis of the major oligosaccharide. Gas chromatography results showed that the oligomer was a hexasaccharide, consisting of rhamnose, galactose, and glucose, in the ratio of 2:3:1, respectively. By weight, the purified hexasaccharide was a fourfold-more-potent inhibitor of coaggregation than the native polysaccharide. Resistance to hydrolysis by sulfuric acid alone and susceptibility to hydrolysis by HF suggested that oligosaccharide chains of the polysaccharide are linked by phosphodiester bonds. Studies with a coaggregation-defective mutant of S. sanguis H1 revealed that the cell walls of the mutant contained neither the polysaccharide nor the hexasaccharide repeating unit. The purification of both a polysaccharide and its constituent hexasaccharide repeating unit, which both inhibited coaggregation, and the absence of this polysaccharide or hexasaccharide on a coaggregation-defective mutant strongly suggest that the hexasaccharide derived from the polysaccharide functions as the receptor for the adhesin from C. ochracea ATCC 33596. 相似文献
83.
Structure of a streptococcal adhesin carbohydrate receptor 总被引:3,自引:0,他引:3
F J Cassels H M Fales J London R W Carlson H van Halbeek 《The Journal of biological chemistry》1990,265(24):14127-14135
Interactions between complementary protein and carbohydrate structures on different genera of human oral bacteria have been implicated in the formation of dental plaque. The carbohydrate receptor on Streptococcus sanguis H1 (one of the primary colonizing species) that is specific for the adhesin on Capnocytophaga ochracea ATCC 33596 (a secondary colonizer) has been isolated from the streptococcal cell wall, purified, and structurally characterized. The hexasaccharide repeating unit of the polysaccharide was purified by reverse-phase, amino-bonded silica, and gel permeation high performance liquid chromatography. Earlier studies established that the repeating unit was a hexasaccharide composed of rhamnose, galactose, and glucose in the ration of 2:3:1, respectively. In the present study, determination of absolute configuration by gas chromatography of the trimethylsilyl (+)-2-butyl glycosides revealed that the rhamnose residues were of the L configuration while the hexoses were all D. 252Californium plasma desorption mass spectrometry of the native, the acetylated and the reduced and acetylated hexasaccharide determined that the molecular mass of the native hexasaccharide was 959, and that the 2 rhamnose residues were linked to each other at the nonreducing terminus of the linear molecule. Methylation analysis revealed the positions of the glycosidic linkages in the hexasaccharide and showed that a galactose residue was present at the reducing end. The structural characterization of the hexasaccharide was completed by one and two dimensional 1H and 13C NMR spectroscopy. Complete 1H and 13C assignments for each glycosyl residue were established by two-dimensional (1H,1H) correlation spectroscopy, homonuclear Hartmann-Hahn, and (13C,1H) correlation experiments. The configurations of the glycosidic linkages were inferred from the chemical shifts and coupling constants of the anomeric 1H and 13C resonances. The sequence of the glycosyl residues was determined by a heteronuclear multiple bond correlation experiment. These data show that the structure of the hexasaccharide repeating unit derived from the cell wall polysaccharide of S. sanguis H1 is: alpha-L-Rhap-(1----2)-alpha-L-Rhap-(1----3)-alpha-D-Galp- (1----3)-beta-D-Galp-(1----4)-beta-D-Glcp-(1----3)-alpha/beta-D-Gal. 相似文献
84.
A new quinolizidine alkaloid, (+)-9α-hydroxymatrine, was isolated from the leaves of Sophora macrocarpa. Its structure was determined by a combination of spectroscopic methods, among which nuclear Overhauser enhancement experiments played a crucial role. Some generalizations are made regarding the mass spectra of matrinoids. 相似文献
85.
The identification and complete assignment of the C-2 and N-1 proton nuclear magnetic resonances (NMR) of the six tryptophan residues of hen lysozyme are reported. Identification of the resonances required a detailed examination of the spectra of the protein in H2O and in 2H2O, and involved the application of spin-echo and Carr-Purcell-Meiboom-Gill pulse sequences. Assignment was achieved by observing the effects on the NMR spectra of performing specific chemical modifications, of binding paramagnetic species (lanthanide ions and spin labels), of binding inhibitors and protons and of carrying out solvent exchange experiments. The problems involved in completion of assignment are fully discussed. In the course of performing experiments to make assignments, several interesting aspects of the behaviour of the tryptophan residues in the protein structure were observed and are discussed. 相似文献
86.
R. Bannach A. Valenzuela B.K. Cassels L. J. Núnez-Vergara H. Speisky 《Cell biology and toxicology》1996,12(2):89-100
Boldine, an aporphine alkaloid, was recently shown by us to exhibit potent antioxidant properties. We report here that boldine concentration-dependently inhibited the peroxidative (accumulation of thiobarbituric acid reactive substances) and lytic damage (trypan blue exclusion and lactate dehydrogenase leakage) to isolated rat hepatocytes induced by tert-butyl hydroperoxide (TBOOH). Boldine (200 mol/L) fully cytoprotected and completely prevented the peroxidation induced by TBOOH a concentrations equal to or lower than 0.87 mmol/L. However, at a peroxide concentration of 0.91 mmol/L, although boldine completely inhibited lipid peroxidation it largely failed to afford cytoprotection against TBOOH. TBOOH alone (0.83 mmol/L) caused an early (within 60 s) sudden decline of reduced glutathione (by 50%) and an equivalent increase in the levels of oxidized glutathione. Neither of these effects was prevented by the simultaneous addition of a cytoprotective and antioxidant concentration of boldine (200 mol/L). The delayed addition of boldine to the suspension (after 10 or 20 min), while effectively blocking any further increase in thiobarbituric acid reactive substances, totally failed to prevent the peroxide-induced loss in cell viability. Conversely, preincubation of the hepatocytes with boldine for 150 min (at which time no boldine could be detected in either intra- or extracellular spaces) prevented lipid peroxidation and was as effective in protecting the cells against the damage caused by the subsequent addition of TBOOH as the simultaneous addition of boldine and TBOOH to hepatocytes preincubated for 150 min under control conditions.Abbreviations DMSO
dimethyl sulfoxide
- GSH
reduced glutathione
- GSSG
oxidized glutathione
- LDH
lactic dehydrogenase
- TBARS
thiobarbituric acid reactive substances
- TBOOH
tert-butyl hydroperoxide 相似文献
87.
Iturriaga-Vásquez P Pérez EG Slater EY Bermúdez I Cassels BK 《Bioorganic & medicinal chemistry》2007,15(10):3368-3372
(S)-Aporphine metho salts with the 1,2,9,10 oxygenation pattern displaced radioligands from recombinant human alpha7 and alpha4beta2 neuronal nicotinic acetylcholine receptors (nAChR) at low micromolar concentrations. The affinity of the nonphenolic glaucine methiodide (4) (vs [(3)H]cytisine) was the lowest at alpha4beta2 nAChR (K(i)=10 microM), and predicentrine methiodide (2) and xanthoplanine iodide (3), with free hydroxyl groups at C-2 or C-9, respectively, had the highest affinity at these receptors (K(i) approximately 1 microM), while the affinity of the diphenolic boldine methiodide (1) was intermediate between these values. At homomeric alpha7 nAChR, xanthoplanine had the highest affinity (K(i)=10 microM) vs [(125)I]alpha-bungarotoxin while the other three compounds displaced the radioligand with K(i) values between 15 and 21 microM. At 100 microM, all four compounds inhibited the responses of these receptors to EC(50) concentrations of ACh. The effects of xanthoplanine iodide (3) were studied in more detail. Xanthoplanine fully inhibited the EC(50) ACh responses of both alpha7 and alpha4beta2 nACh receptors with estimated IC(50) values of 9+/-3 microM (alpha7) and 5+/-0.8 microM (alpha4beta2). 相似文献
88.
Maya JD Cassels BK Iturriaga-Vásquez P Ferreira J Faúndez M Galanti N Ferreira A Morello A 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2007,146(4):601-620
Current knowledge of the biochemistry of Trypanosoma cruzi has led to the development of new drugs and the understanding of their mode of action. Some trypanocidal drugs such as nifurtimox and benznidazole act through free radical generation during their metabolism. T. cruzi is very susceptible to the cell damage induced by these metabolites because enzymes scavenging free radicals are absent or have very low activities in the parasite. Another potential target is the biosynthetic pathway of glutathione and trypanothione, the low molecular weight thiol found exclusively in trypanosomatids. These thiols scavenge free radicals and participate in the conjugation and detoxication of numerous drugs. Inhibition of this key pathway could render the parasite much more susceptible to the toxic action of drugs such as nifurtimox and benznidazole without affecting the host significantly. Other drugs such as allopurinol and purine analogs inhibit purine transport in T. cruzi, which cannot synthesize purines de novo. Nitroimidazole derivatives such as itraconazole inhibit sterol metabolism. The parasite's respiratory chain is another potential therapeutic target because of its many differences with the host enzyme complexes. The pharmacological modulation of the host's immune response against T. cruzi infection as a possible chemotherapeutic target is discussed. A large set of chemicals of plant origin and a few animal metabolites active against T. cruzi are enumerated and their likely modes of action are briefly discussed. 相似文献
89.
Changes in ionized calcium were studied in axons isolated from living squid by measuring absorbance of the Ca binding dye Arsenazo III using multiwavelength differential absorption spectroscopy. Absorption changes measured in situ were calibrated in vitro with media of ionic composition similar to axoplasm containing CaEGTA buffers. Calcium loads of 50-2,500 μmol/kg axoplasm were induced by microinjection, by stimulation in 112 mM Ca seawater, or by soaking in choline saline with 1-10 mM Ca. Over this range of calcium loading of intact axoplasm, the ionized calcium in the axoplasm rose about 0.6 nM/μM load. Similar loading in axons preteated with carbonyl cyanide 4- trifluoromethoxyphenylhydrazone (FCCP) to inhibit the mitochondrial proton gradient increased ionized calcium by 5-7 percent of the imposed load, i.e. 93-95 percent of the calcium load was buffered by a process insensitive to FCCP. This FCCP- insensitive buffer system was not saturated by the largest calcium loads imposed, indicating a capacity of at least several millimolar. Treatment of previously loaded axons with FCCP or apyrase plus cyanide produced rises in ionized calcium which could be correlated with the extent of the load. Analysis of results indicated that, whereas only 6 percent of the endogenous calcium in fresh axons is stored in the FCCP-sensitive (presumably mitochondrial) buffer system, about 30 percent of an imposed exogenous load in the range of 50-2,500 μM is taken up by this system. 相似文献
90.
Asensio JL; Canada FJ; Bruix M; Gonzalez C; Khiar N; Rodriguez-Romero A; Jimenez-Barbero J 《Glycobiology》1998,8(6):569-577
The specific interaction of hevein with GlcNAc-containing oligosaccharides
has been analyzed by1H-NMR spectroscopy. The association constants for the
binding of hevein to a variety of ligands have been estimated from1H-NMR
titration experiments. The association constants increase in the order
GlcNAc-alpha(1-->6)-Man < GlcNAc < benzyl-beta-GlcNAc <
p-nitrophenyl-beta-GlcNAc < chitobiose < p-
nitrophenyl-beta-chitobioside < methyl-beta-chitobioside <
chitotriose. Entropy and enthalpy of binding for different complexes have
been obtained from van't Hoff analysis. The driving force for the binding
process is provided by a negative DeltaH0which is partially compensated by
negative DeltaS0. These negative signs indicate that hydrogen bonding and
van der Waals forces are the major interactions stabilizing the complex.
NOESY NMR experiments in water solution provided 475 accurate protein
proton-proton distance constraints after employing the MARDIGRAS program.
In addition, 15 unambiguous protein/carbohydrate NOEs were detected. All
the experimental constraints were used in a refinement protocol including
restrained molecular dynamics in order to determine the highly refined
solution conformation of this protein- carbohydrate complex. With regard to
the NMR structure of the free protein, no important changes in the protein
nOe's were observed, indicating that carbohydrate-induced conformational
changes are small. The average backbone rmsd of the 20 refined structures
was 0.055 nm, while the heavy atom rmsd was 0.116 nm. It can be deduced
that both hydrogen bonds and van der Waals contacts confer stability to the
complex. A comparison of the three-dimensional structure of hevein in
solution to those reported for wheat germ agglutinin (WGA) and hevein
itself in the solid state has also been performed. The polypeptide
conformation has also been compared to the NMR-derived structure of a
smaller antifungical peptide, Ac-AMP2.
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