共查询到20条相似文献,搜索用时 31 毫秒
1.
Issei Doi Masaki Kuse Toshio Nishikawa Minoru Isobe 《Bioorganic & medicinal chemistry》2009,17(9):3399-3404
During the course of protein modification program, we employed a recombinant aequorin, the apo-protein reconstituted with coelenterazine, and found out that the photolytic hyperperoxide modified three –S–SCH2CHOHCHOHCH2SH groups to –S–SCH2CHOHCHCH–SO)H or –S–SCH2CHOHCHCH–S(O)OH of terminal DTT connected to cysteine residues of the C145, C152 and C180, which turned out to locate near the chromophore. 相似文献
2.
《生物化学与生物物理学报:生物膜》2018,1860(2):292-299
Lensoside Aβ, representing the flavonol glycosides, is a compound isolated from the aerial parts of edible lentil (Lens culinaris) cultivar Tina. This substance arouses interest because so far there is very little data about secondary metabolites isolated from the leaves and stems of this plant. Additionally, bioactive potential of flavonoids is directly coupled with the membranes as a primary target of their physiological and pharmacological activity. The aim of this study was to investigate the effect of lensoside Aβ on lipid membranes. Interaction of examined compound with liposomes formed with dipalmitoylphosphatidylcholine (DPPC) was investigated with application of FTIR spectroscopy and 1H NMR technique. Molecular localization and orientation of lensoside Aβ in a single lipid bilayer system represented by giant unilamellar vesicles, was also investigated with application of confocal fluorescence lifetime imaging microscopy (FLIM).FTIR analysis revealed that the tested compound incorporates into DPPC membranes via hydrogen bonding to lipid polar head groups in the PO2 group region and the COPOC segment. Furthermore 1H NMR analysis showed ordering effect in both the hydrophobic alkyl chains region and the polar heads of phospholipids. FLIM investigation has revealed roughly parallel orientation of its molecules in the membranes. This suggests that one of the possible physiological functions of this flavonol could be screening a cell against short-wavelength radiation. 相似文献
3.
Interactions of melatonin with zwitterionic dipalmitoyl phosphatidylcholine (DPPC) multilamellar liposomes (MLVs) were investigated as a function of temperature and melatonin concentration (1-30 mol%) by using two noninvasive techniques, namely Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). The investigation of the C-H, CO, and PO2− antisymmetric double stretching modes in FTIR spectra and DSC studies reveal that melatonin changes the physical properties of the DPPC bilayers by decreasing the main phase transition temperature, abolishing the pretransition, ordering the system in the gel phase, and increasing the dynamics of the system both in the gel and liquid crystalline phases. It also causes significant decrease in the wavenumber for the CO stretching and PO2− antisymmetric double bond stretching bands, which indicates strong hydrogen bonding The results imply that melatonin locates in the interfacial region of the membrane. Furthermore, in the DSC curve, more than one signal is observed at high melatonin concentrations (24 and 30 mol%), which indicates melatonin-induced phase separation in DPPC membranes. 相似文献
4.
Siegfried S.F. Leung Julian Tirado-Rives William L. Jorgensen 《Bioorganic & medicinal chemistry letters》2009,19(4):1236-1239
To seek vancomycin analogs with broader antibacterial activity, effects of backbone modifications for the agylcon 2 on binding with d-Ala-d-Ala- and d-Ala-d-Lac-containing peptides were investigated by Monte Carlo/free energy perturbation (MC/FEP) calculations. The experimental trend in binding affinities for 2 with three tripeptides was well reproduced. Possible modifications of the peptide bond between residues 4 and 5 were then considered, specifically for conversion of the OCNH linkage to CH2NH2+ (6), FCCH (7), HCCH (8), and HNCO (9). The MC/FEP results did not yield binding improvements for 7, 8, and 9, though the fluorovinyl replacement is relatively benign. The previously reported analog 6 remains as the only variant that exhibits improved affinity for the d-Ala-d-Lac sequence and acceptable affinity for the d-Ala-d-Ala sequence. 相似文献
5.
Reductions of (Z)-C6H5CHCXC(O)CH3 (X = Cl, Br) mediated by Saccharomyces cerevisiae, Candida albicans, Rhodotorula glutinis, Geotrichum candidum and Micrococcus luteus gave the corresponding halohydrins through consecutive reduction reactions of CC and CO bonds. In general, the reactions performed in the biphasic system water/[(bmim)PF6] gave better diastereoselectivity and enantioselectivity than in pure water. 相似文献
6.
《Bio Systems》2008,91(3):792-801
We have investigated the roles played by CH⋯OC interactions in RNA binding proteins. There was an average of 78 CH⋯OC interactions per protein and also there was an average of one significant CH⋯OC interaction for every 6 residues in the 59 RNA binding proteins studied. Main chain–Main chain (MM) CH⋯OC interactions are the predominant type of interactions in RNA binding proteins. The donor atom contribution to CH⋯OC interactions was mainly from aliphatic residues. The acceptor atom contribution for MM CH⋯OC interactions was mainly from Val, Phe, Leu, Ile, Arg and Ala. The secondary structure preference analysis of CH⋯OC interacting residues showed that, Arg, Gln, Glu and Tyr preferred to be in helix, while Ala, Asp, Cys, Gly, Ile, Leu, Lys, Met, Phe, Trp and Val preferred to be in strand conformation. Most of the CH⋯OC interacting polar amino acid residues were solvent exposed while, majority of the CH⋯OC interacting non polar residues were excluded from the solvent. Long and medium-range CH⋯OC interactions are the predominant type of interactions in RNA binding proteins. More than 50% of CH⋯OC interacting residues had a higher conservation score. Significant percentage of CH⋯OC interacting residues had one or more stabilization centers. Sixty-six percent of the theoretically predicted stabilizing residues were also involved in CH⋯OC interactions and hence these residues may also contribute additional stability to RNA binding proteins. 相似文献
7.
In this study, we examined the mechanisms and kinetic profiles of intracellular nitrosative processes using diaminofluorescein (DAF-2) as a target in RAW 264.7 cells. The intracellular formation of the fluorescent, nitrosated product diaminofluorescein triazol (DAFT) from both endogenous and exogenous nitric oxide (NO) was prevented by deoxygenation and by cell membrane-permeable superoxide (O2−) scavengers but not by extracellular bovine Cu,Zn-SOD. In addition, the DAFT formation rate decreased in the presence of cell membrane-permeable Mn porphyrins that are known to scavenge peroxynitrite (ONOO−) but was enhanced by HCO3−/CO2. Together, these results indicate that nitrosative processes in RAW 264.7 cells depend on endogenous intracellular O2− and are stimulated by ONOO−/CO2-derived radical oxidants. The N2O3 scavenger sodium azide (NaN3) only partially attenuated the DAFT formation rate and only with high NO (>120 nM), suggesting that DAFT formation occurs by nitrosation (azide-susceptible DAFT formation) and predominantly by oxidative nitrosylation (azide-resistant DAFT formation). Interestingly, the DAFT formation rate increased linearly with NO concentrations of up to 120–140 nM but thereafter underwent a sharp transition and became insensitive to NO. This behavior indicates the sudden exhaustion of an endogenous cell substrate that reacts rapidly with NO and induces nitrosative processes, consistent with the involvement of intracellular O2−. On the other hand, intracellular DAFT formation stimulated by a fixed flux of xanthine oxidase-derived extracellular O2− that also occurs by nitrosation and oxidative nitrosylation increased, peaked, and then decreased with increasing NO, as previously observed. Thus, our findings complementarily show that intra- and extracellular O2−-dependent nitrosative processes occurring by the same chemical mechanisms do not necessarily depend on NO concentration and exhibit different unusual kinetic profiles with NO dynamics, depending on the biological compartment in which NO and O2− interact. 相似文献
8.
《Inorganica chimica acta》1988,144(1):57-61
The complex [PtCIMe(i-PrNCHCHNi-Pr)] and its unstable five-coordinate ethylene adduct have been prepared and characterized by 1H NMR. The crystal and molecular structure of the former has been determined. The complex crystallizes in the orthorhombic space group Pca2 1, with a = 12.138(6), b = 9.601(6), c = 10.586(6)Å, Z = 4. Refinement converged to a final R index of 0.059. The geometrical parameters of the structure are compared with those of a related complex and discussed in relation to the stability of the five-coordinate olefin adducts. 相似文献
9.
Physiological processes are often activated by reactive oxygen species (ROS), such as the superoxide anion (O2–) and nitric oxide (NO) produced by cells. We studied the interactions between NO and O2–, and their generators (NO synthase, NOS, and a still elusive oxidase), in human spermatozoa during capacitation (transformations needed for acquisition of fertility). Albumin, fetal cord serum ultrafiltrate, and L-arginine triggered capacitation and ROS generation (NO and O2–) and superoxide dismutase (SOD) and NOS inhibitors prevented all these effects. Surprisingly, capacitation due to exogenous NO (or O2–) was also blocked by SOD (or NOS inhibitors). Probes used were proven specific and innocuous on spermatozoa. Whereas O2– was needed only for 30 min, the continuous NO generation was essential for hours. Capacitation caused a time-dependent increase in protein tyrosine nitration that was prevented by SOD and NOS inhibitors, suggesting that O2– and NO· also act via the formation of ONOO–. Spermatozoa treated with NO (or O2–) initiated a dose-dependent O2– (or NO) production, providing, for the first time in cells, a strong evidence for a two-sided ROS-induced ROS generation. Data presented show a close interaction between NO and O2– and their generators during sperm capacitation. 相似文献
10.
Jianguo Zhang Huihui Zheng Tonglai Zhang Lina Feng 《Inorganica chimica acta》2008,361(14-15):4143-4147
Molecular structure, vibrational frequencies and infrared intensities of 1,1,3,3,5,5,7,7-octaazido-cyclo-tetraphosphazene have been studied employing HF, B3LYP and B3PW91 methods using 6-31G1 basis set. The study showed that this molecule has non-planar structure and there is no imaginary frequency. Furthermore, there exist four sets of special PN bonds in the P4N28 ring; the PN bonds and the azide groups conjoint to them have special characters. The NBO population analysis was used to help us understand the interactions between donor orbit and acceptor orbit in the nitrogen phosphorus systems. Furthermore, three methods with the same basis set are further employed to calculate the heats of formation for the compound. 相似文献
11.
12.
Endothelial dysfunction causes an imbalance in endothelial NO and O2− production rates and increased peroxynitrite formation. Peroxynitrite and its decomposition products cause multiple deleterious effects including tyrosine nitration of proteins, superoxide dismutase (SOD) inactivation, and tissue damage. Studies have shown that peroxynitrite formation during endothelial dysfunction is strongly dependent on the NO and O2− production rates. Previous experimental and modeling studies examining the role of NO and O2− production imbalance on peroxynitrite formation showed different results in biological and synthetic systems. However, there is a lack of quantitative information about the formation and biological relevance of peroxynitrite under oxidative, nitroxidative, and nitrosative stress conditions in the microcirculation. We developed a computational biotransport model to examine the role of endothelial NO and O2− production on the complex biochemical NO and O2− interactions in the microcirculation. We also modeled the effect of variability in SOD expression and activity during oxidative stress. The results showed that peroxynitrite concentration increased with increase in either O2− to NO or NO to O2− production rate ratio (QO2−/QNO or QNO/QO2−, respectively). The peroxynitrite concentrations were similar for both production rate ratios, indicating that peroxynitrite-related nitroxidative and nitrosative stresses may be similar in endothelial dysfunction or inducible NO synthase (iNOS)-induced NO production. The endothelial peroxynitrite concentration increased with increase in both QO2−/QNO and QNO/QO2− ratios at SOD concentrations of 0.1–100 μM. The absence of SOD may not mitigate the extent of peroxynitrite-mediated toxicity, as we predicted an insignificant increase in peroxynitrite levels beyond QO2−/QNO and QNO/QO2− ratios of 1. The results support the experimental observations of biological systems and show that peroxynitrite formation increases with increase in either NO or O2− production, and excess NO production from iNOS or from NO donors during oxidative stress conditions does not reduce the extent of peroxynitrite mediated toxicity. 相似文献
13.
Nguyen Tien An Do Truong Thien Nguyen Thi Dong Pham Le Dung 《Carbohydrate polymers》2009,75(3):489-497
In this work, only N-substituted chitosan derivatives (water-soluble N-carboxymethylchitosan derivatives: N-CMC) with different degrees of substitution were obtained by reaction of a fully deacetylated chitosan (derived from deacetylation of chitosan using decrystallized method) with monochloroacetic acid at pH 8 and temperature of 90 °C. The structure of N-carboxymethylchitosan and chitosan was characterized by IR, 1H, 13C and 1H–13C NMR-HSQC spectra. In the IR spectrum of the N-carboxymethylchitosan, the appearance of peak at 1742 cm?1 was assigned for CO group of NHCH2COOH of substituted chitosan. In the 1H NMR spectra, the peaks at about 3.81÷4.06 ppm, assigned for CH2 groups of NHCH2 and N(CH2)2, were the major feature, while in the 1H–13C NMR-HSQC spectra, signals of CH2 confirmed the presence of these two different substituted CH2 groups. The degree of substitution (DS) of N-monosubstitution (DSN-mono) decreased from 0.47 to 0.03 meanwhile that of N,N-disubstitution (DSN,N-di) increased from 0.52 to 0.96 since the mass ratio of chitosan/monochloroacetic acid changing from 1/1 to 1/4. The N-carboxymethylchitosan derivatives have been used for adsorption Cu(II) ion from aqueous solution. The results shown that the optimum conditions for adsorption Cu(II) ion in nitrate solution were pH 6.5, temperature of 30 °C, for 60–90 min and the substituted chitosan derivative having DSN-mono of 0.16 and DSN,N-di of 0.81 had maximum adsorption capacity of 192 mg Cu(II) per gram of N-CMC. 相似文献
14.
《Bioorganic & medicinal chemistry letters》2019,29(16):2145-2149
Scavenging abilities of animal sera against six reactive species (OH, O2−, RO, t-BuOO, H3C, and 1O2) were determined with the use of multiple free-radical scavenging (MULTIS) method. Commercially available sera from pig, horse, rabbit, Guinea pig, hamster and chicken were subjected to MULTIS analysis and the results were compared with human specimen. In general, animal sera showed lower scavenging ability against OH and RO radicals than human serum. However, it is noteworthy that rabbit and chicken sera have higher scavenging ability against O2− than others. This is consistent with the known data that superoxide dismutase levels in these sera are high. In addition, we determined the uric acid level in animal sera using the uricase-TOOS method. In chicken serum, uric acid was found to be the major effective component in RO scavenging. This paper is first to quantitatively evaluate antioxidant capacities in animal sera. 相似文献
15.
《生物化学与生物物理学报:生物膜》2019,1861(4):810-818
Simvastatin is a lipid-lowering drug in the pharmaceutical group statins. Interaction of a drug with lipids may define its role in the system and be critical for its pharmacological activity. We examined the interactions of simvastatin with zwitterionic dipalmitoyl phosphatidylcholine (DPPC) and anionic dipalmitoyl phosphatidylglycerol (DPPG) multilamellar vesicles (MLVs) as a function of temperature at different simvastatin concentrations using Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). The FTIR results indicate that the effect of simvastatin on membrane structure and dynamics depends on the type of membrane lipids. In anionic DPPG MLVs, high simvastatin concentrations (12, 18, 24 mol%) change the position of the CH2 antisymmetric stretching mode to lower wavenumber values, implying an ordering effect. However, in zwitterionic DPPC MLVs, high concentrations of simvastatin disorder systems both in the gel and liquid crystalline phases. Moreover, in DPPG and DPPC MLVs, simvastatin has opposite dual effects on membrane dynamics. The bandwidth of the CH2 antisymmetric stretching modes increases in DPPG MLVs, implying an increase in the dynamics, whereas it decreases in DPPC MLVs. Simvastatin caused broadening of the phase transition peaks and formation of shoulders on the phase transition peaks in DSC curves, indicating multi-domain formations in the phospholipid membranes. Because physical features of membranes such as lipid order and fluidity may be changed with the bioactivity of drugs, opposing effects of simvastatin on the order and dynamics of neutral and charged phospholipids may be critical to deduce the action mechanism of the drug and estimate drug-membrane interactions. 相似文献
16.
The human cholesteryl ester transfer protein (CETP) transfers cholesteryl ester from high-density lipoprotein (HDL) to other lipoproteins and has been established as an attractive target for reducing the risk of atherosclerosis. Here, an amphipathic α-helix peptide, namely SBH-peptide (465EHLLVDFLQSLS476), was derived from the C-terminal tail of CETP. The peptide exhibits self-binding capability towards the CETP. Crystal structure analysis, molecular dynamics (MD) simulations and ab initio electron correlation characterizations of CETP–SBH-peptide complex system revealed that the Phe471 residue plays a key role in SBH-peptide binding, which can form a π-π stacking with the Phe197 residue of CETP. In addition, substitution of the hydrogen atom H4 of Phe471 with halogen atoms, in particular the bromine atom Br4, can constitute a geometrically satisfactory halogen bonding with the oxygen atom O of CETP Ile193 residue. Fluorescence polarization assays substantiated that (i) mutation of the aromatic Phe471 to small Ala residue would impair the SBH-peptide affinity with Kd change from 10.5 to 26.4 μM, indicating that the π-π stacking should exist in Phe471⋯Phe197 adduct, and (ii) substitution with Br4 can considerably improve SBH-peptide affinity by ∼3-fold, but the SBH-peptide binding does not change essentially upon substitution with Br3 (a negative control that is theoretically unable to form the halogen bonding), indicating that the rationally designed halogen bonding should form between the Phe471(Br4) residue of SBH-peptide and the Ile193 residue of CETP protein. 相似文献
17.
《Inorganica chimica acta》1988,148(1):71-84
Os3(CO)10(MeCN)2 reacts at room temperature in MeCN or toluene with R-Pyca2 to yield two isomers of Os3(CO)10(R-Pyca) that differ in the bonding of the R-Pyca ligand to the Os3(CO)10 unit. In all cases Os3(CO)10(R-Pyca(4e)) (isomer A; 4a: R = c-Pr, 4b: R = i-Pr, 4c: R = neo-Pent, 4d: R = t-Bu), containing a chelating 4e donating R-Pyca ligand and three OsS bonds, could be isolated. In the case of R = c-Pr and R = i-Pr Os3(CO)10(R-Pyca(6e)) (isomer B; 5a: R = c-Pr, 5b: R = i-Pr), in which only two OsS bonds are present and the R-Pyca ligand is bonded as a 6e donating ligand bridging two non-bonded Os atoms, could be isolated as a minor product.At 70 °C Os3(CO)10(R-Pyca(4e)) (4b and 4d) loses one carbonyl and the pyridine moiety of the R-Pyca ligand is ortho-metallated to form HOs3(C5H3N-2-C(H)NR)(CO)9 (6b: R = i-Pr and 6d: R = t-Bu). Under the same conditions Os3(CO)10(i-Pr-Pyca(6e)) (5b) reacts to Os2(CO)6(6e)) (7b) containing a bridging 6e donating ligands. The latter two reactions were followed with FT-IR spectroscopy in a high temperature IR cell.The structure of the complexes in solution have been studied by 1H and 1C NMR and IR spectroscopy. The stoichiometries of 4a and 5a were determined by FAB-mass spectrometry while an exact mass determination was carried out for 4a.The crystal structure of 6b has been determined. Crystal of 6b are monoclinic, space group P21/n, with a = 7.808(2),b = 17.613(3),c = 16.400(8)Å, β = 94.09(3)° and Z = 4. The structure was refined to R = 0.039. The molecule contains a triangular array of osmium atoms [Os(1)Os(2) = 2.898(2)Å, Os(1)Os(3) = 2.886(2)Åand Os(2)O(3) = 2.911(2)Å] and nine terminally bonded carbonyl ligands. The C5H3N-2-C(H)N-i-Pr ligand is chelate bonded to Os(2) with the pyridine and imine nitrogens atoms axially and equatorially coordinated respectively [Os(2)N(1) = 2.00(2)Åand Os(2)N(2) = 2.11(2)Å]. The i-Pr-Pyca ligand is ortho-metallated at C(1) and forms a four membered ring containing Os(2), Os(3), C(1) and N(1), the Os(3)C(1) distance being 2.12(2)Å. The hydride, which could not be located unequivocally from a difference Fourier map is proposed to bridge the Os(2)(3) bond on the basis of stereochemical considerations. 相似文献
18.
Gorka San José Julen Bidegain Pablo A. Robador Javier Díez Ana Fortuño Guillermo Zalba 《Free radical biology & medicine》2009,46(8):1058-1067
Insulin stimulates superoxide (O2?) production in monocytes and macrophages. However, the mechanisms through which insulin induces O2? production are not completely understood. In this study, we (a) characterized the enzyme and the pathways involved in insulin-stimulated O2? production in human monocytes and murine macrophages, and (b) analyzed the consequences of insulin-stimulated O2? production on the cellular phenotype in these cells. We showed that insulin stimulated O2? production, and promoted p47phox translocation to the plasma membrane. Insulin-induced O2? production and p47phox translocation were prevented in the presence of specific inhibitors of PI3K and PKC. Insulin-mediated NADPH oxidase activation stimulated MMP-9 activation in monocytes and cell proliferation in macrophages. The effect of insulin on these phenotypic responses was mediated through NFκB, p38MAPK, and ERK 1/2 activation. Small-interfering RNA-specific gene silencing targeted specifically against Nox2 reduced the cognate protein expression, decreased insulin-induced O2? production, inhibited the turn on of NFκB, p38MAPK, and ERK 1/2, and reduced cell proliferation in macrophages. These findings suggest a pivotal role for NADPH oxidase in insulin-induced proliferation and proteolytic activation in monocytes and macrophages, respectively, and identify a pathway that may play a pathological role in hyperinsulinemic states. 相似文献
19.
《Biochimica et Biophysica Acta (BBA)/General Subjects》2002,1573(2):156-164
The effect of the chemical structure of nitroxyl spin probes on the rate at which ESR signals are lost in the presence of reactive oxygen species (ROS) was examined. When the spin probes were reacted with either hydroxyl radical (OH) or superoxide anion radical (O2−) in the presence of cysteine or NADH, the probes lost ESR signal depending on both their ring structure and substituents. Pyrrolidine nitroxyl probes were relatively resistant to the signal decay caused by O2− with cysteine/NADH. Signal decay rates for these reactions correlated with reported redox potentials of the nitroxyl/oxoammonium couple of spin probes, suggesting that the signal decay mechanism in both cases involves the oxidation of a nitroxyl group. The apparent rate constants of the reactions between the spin probe and OH and between the spin probe and O2− in the presence of cysteine were estimated using mannitol and superoxide dismutase (SOD), respectively, as competitive standards. The rate constants for spin probes and OH were in the order of 109 M−1 s−1, much higher than those for the probes and O2− in the presence of cysteine (103–104 M−1 s−1). These basic data are useful for the measurement of OH and O2− in living animals by in vivo ESR spectroscopy. 相似文献
20.
Precise spatiotemporal regulation of O2−-generating NADPH oxidases (Nox) is a vital requirement. In the case of Nox1–3, which depend on the small GTPase Rac, acceleration of GTP hydrolysis by GTPase activating protein (GAP) could represent a feasible temporal control mechanism. Our goal was to investigate the molecular interactions between RacGAPs and phagocytic Nox2 in neutrophilic granulocytes. In structural studies we revealed that simultaneous interaction of Rac with its effector protein p67phox and regulatory protein RacGAP was sterically possible. The effect of RacGAPs was experimentally investigated in a cell-free O2−-generating system consisting of isolated membranes and recombinant p47phox and p67phox proteins. Addition of soluble RacGAPs decreased O2− production and there was no difference in the effect of four RacGAPs previously identified in neutrophils. Depletion of membrane-associated RacGAPs had a selective effect: a decrease in ARHGAP1 or ARHGAP25 level increased O2− production but a depletion of ARHGAP35 had no effect. Only membrane-localized RacGAPs seem to be able to interact with Rac when it is assembled in the Nox2 complex. Thus, in neutrophils multiple RacGAPs are involved in the control of O2− production by Nox2, allowing selective regulation via different signaling pathways. 相似文献