共查询到20条相似文献,搜索用时 15 毫秒
1.
By introducing cell membrane into electrophoretic buffer as pseudo-stationary phase, a novel capillary electrophoresis method was established to explore the interaction between drugs and cell membrane, where the interaction between citalopram and rabbit red blood cell membrane was used as an example. A series of concentrations of cell membrane were suspended into the running buffer by peak-shift method. The binding constant of citalopram to rabbit red blood cell membrane of 0.977 g?1·L was obtained after treatment of Scatchard plot. This method could provide not only a new way for the investigation on the interactions between drugs and cell membrane, but also a new approach for high throughput screening of the drug membrane permeability, biological activity, and evaluating drugs in vivo. 相似文献
2.
3.
We present an investigation of structural dynamics in excited-state cations probed in real-time by femtosecond time-resolved ion photofragmentation spectroscopy. From photoelectron spectroscopy data on 1,3-dibromopropane we conclude that the pump pulse ionizes the molecule, populating an excited electronic state of the radical cation. In this state a coherent torsional vibration of the bromomethylene groups with a period of 700 fs is started and probed by photoinduced fragmentation of the molecular cation. The vibrational coherence dephases with the decay of the excited state to the ground state of the cation in 1.6 ps. The real-time probing of the excited-state dynamics is made possible by exploiting the interaction between the two bromine chromophores and its dependence on molecular conformation. This experiment therefore illustrates the applicability of the concept of probing ultrafast molecular dynamics using the intramolecular interaction between two chromophores. 相似文献
4.
Amphotericin B (AmB) is a well-known polyene macrolide antibiotic used to treat systemic fungal infections. According to a well-documented hypothesis, molecules of AmB form ionic membrane channels that are responsible for chemotherapeutic action. These channels disturb the barrier function of the cell membrane which, in consequence, leads to cell death. The presence of sterols in the cell membrane is necessary for full manifestation of the antibiotic's ionophoric activity, at least in vivo. Ergosterol-containing fungal membranes are targeted more efficiently by AmB than mammalian membranes containing cholesterol. However, a similar level of disturbance of fungal and mammalian membranes is responsible for serious toxicity of the antibiotic. Due to the importance of AmB and lack of better antifungal alternatives, the search for new less toxic derivatives of this antibiotic still continues. Therefore, studies of the AmB-membrane interaction are very important. The present work constitutes a continuation of a broad program of study on AmB mode of action in our group. In particular, molecular dynamics simulations of AmB monomers inside the bilayers of three different compositions (pure dimiristoylphosphatidylcholine (DMPC) and DMPC bilayer containing approximately 25 mol % of cholesterol or ergosterol) were carried out. In general, analysis of generated trajectories resulted in identifying many significant differences in the behavior of AmB monomers depending on the membrane environment. In particular, it was established that the antibiotic increases the internal order of DMPC bilayer containing 25 mol % of cholesterol, while it has no effect on the order of the bilayer with the same amount of ergosterol. Performed calculations also revealed that relatively rigid and elongated AmB molecules exhibit higher affinity toward the sterol-containing lo phases and, therefore, may be cumulated in ordered membrane domains (e.g., lipid rafts). Since the partition coefficient between the ld and lo phase appears to be greater in the case of the ergosterol- compared to cholesterol-containing membrane, this effect can be also discussed as the possible origin of AmB-selective toxicity and indirect sterol involvement in expression of AmB activity. 相似文献
5.
Beales PA Bergstrom CL Geerts N Groves JT Vanderlick TK 《Langmuir : the ACS journal of surfaces and colloids》2011,27(10):6107-6115
We present a novel platform for investigating the composition-specific interactions of proteins (or other biologically relevant molecules) with model membranes composed of compositionally distinct domains. We focus on the interaction between a mitochondrial-specific lipid, cardiolipin (CL), and a peripheral membrane protein, cytochrome c (cyt c). We engineer vesicles with compositions such that they phase separate into coexisting liquid phases and the lipid of interest, CL, preferentially localizes into one of the domains (the liquid disordered (L(d)) phase). The presence of CL-rich and CL-depleted domains within the same vesicle provides a built-in control experiment to simultaneously observe the behavior of two membrane compositions under identical conditions. We find that cyt c binds strongly to CL-rich domains and observe fascinating morphological transitions within these regions of membrane. CL-rich domains start to form small buds and eventually fold up into a collapsed state. We also observe that cyt c can induce a strong attraction between the CL-rich domains of adjacent vesicles as demonstrated by the development of large osculating regions between these domains. Qualitatively similar behavior is observed when other polycationic proteins or polymers of a similar size and net charge are used instead of cyt c. We argue that these striking phenomena can be simply understood by consideration of colloidal forces between the protein and the membrane. We discuss the possible biological implications of our observations in relation to the structure and function of mitochondria. 相似文献
6.
Synthetic control over the dynamics of mesoscaled cargo release from colloidal polymer vectors inside live cells
下载免费PDF全文
![点击此处可从《Journal of polymer science. Part A, Polymer chemistry》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Harvind S. Chahal Dev S. Chahal Patrick M. McBride Brett A. Helms 《Journal of polymer science. Part A, Polymer chemistry》2015,53(2):256-264
Directed delivery of mesoscaled cargo—for example, nanocrystals, proteins, or nucleic acids—to cells using polymer vectors impacts numerous biomedical fields. We introduce here the concept of dynamic complementarity as a simple, yet powerful approach to control the rate of mesoscaled cargo dissociation from colloidal polymer vectors once inside the cytosol. By tuning the degree of electrostatic reciprocity between the polymer vector and its cargo, it is possible to both deliver and release large cargo in live cells in a controllable manner over both long and short periods, pointing to a highly modular materials platform with molecularly tailored properties suited to task. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 256–264 相似文献
7.
Caballero J Zamora C Aguayo D Yañez C González-Nilo FD 《The journal of physical chemistry. B》2008,112(33):10194-10201
The interaction of progesterone with beta-cyclodextrin (beta-CD) was studied by differential pulse polarography. The aim of the present work was to study the effect of beta-CD on the electrochemical behavior of progesterone in aqueous solution and also to analyze the molecular interactions involved in formation of the inclusion complex. The complex with stoichiometry of 1:1 was thermodynamically characterized. In addition, steered molecular dynamics (SMD) was used to investigate the energetic properties of formation of the inclusion complex along four different pathways (reaction coordinates), considering two possible orientations. From multiple trajectories along these pathways, the potentials of mean force for formation of the beta-CD progesterone inclusion complex were calculated. The energy analysis was in good agreement with the experimental results. In the beta-CD progesterone inclusion complex, a large portion of the steroid skeleton is included in the beta-CD cavity. The lowest energy was found when the D-ring of the guest molecule is located near the secondary hydroxyls of the beta-CD cavity. In the most probable orientation, one intermolecular hydrogen bond is formed between the O of the C-20 keto group of the progesterone and a secondary hydroxyl of the beta-CD. 相似文献
8.
Membrane proteins, although constituting about one-third of all proteins encoded by the genomes of living organisms, are still strongly underrepresented in the database of 3D protein structures, which reflects the big challenge presented by this class of proteins. Structural biologists, by employing electron and x-ray approaches, are continuously revealing new and fundamental insights into the structure, function, assembly and interaction with lipids of membrane proteins. To date, two structural motifs, alpha-helices and beta-sheets, have been found in membrane proteins and interestingly these two structural motives correlate with the location: while alpha-helical bundles are most often found in the receptors and ion channels of plasma and endoplasmic reticulum membranes, beta-barrels are restricted to the outer membrane of Gram-negative bacteria and in the mitochondrial membrane, and represent the structural motif used by several microbial toxins to form cytotoxic transmembrane channels. The beta-barrel, while being a rigid and stable motif is a versatile scaffold, having a wide variation in the size of the barrel, in the mechanism to open or close the gate and to impose selectivity on substrates. Even if the number of x-ray structures of integral membrane proteins has greatly increased in recent years, only a few of them provide information at a molecular level on how proteins interact with lipids that surround them in the membrane. The detailed mechanism of protein lipid interactions is of fundamental importance for understanding membrane protein folding, membrane adsorption, insertion and function in lipid bilayers. Both specific and unspecific interactions with lipids may participate in protein folding and assembly. 相似文献
9.
The interactions between drug molecules and membrane were studied using the new chromatography stationary phase of liposome coated zirconia–magnesia. log Ks(ZrO2–MgO) on this new chromatography for some drugs, compared with that on liposome coated silica chromatography and other reported data, fair correlations were observed between them when excluding effect of special adsorption. log Ks(ZrO2–MgO) values for barbitalum, diazepam, benzene, benzocaine and toluene correlated well with corresponding values on liposome coated silica chromatography (R = 0.99778, P < 0.001; R = 0.98229, P < 0.003; R = 0.9985, P < 0.0001; R = 0.99925, P < 0.0001, pH value of mobile phase at pH 7.4, 7.0, 6.4 and 5.4, respectively). They also correlated well with the literature data on immobilized artificial membrane chromatography (R = 0.99999, P < 0.004 at pH 7.4) and liposome chromatography (R = 0.99994, P < 0.008) for procaine, lidocaine and bupivacaine. Liposome coated zirconia–magnesia chromatography can thus be used for studying drug–membrane interaction and prediction of drug absorption as another liposome chromatography method. 相似文献
10.
纳米雄黄与脂质体仿生膜的相互作用研究 总被引:2,自引:0,他引:2
本工作以卵磷脂与胆固醇组成的磷脂小单层脂质体(small unilamelarvesicles,suv)作为仿生膜的简单模型,采用表面等离子共振技术(SPR)、荧光偏振、拉曼(Raman)光谱、核磁共振(NMR)及原子力显微镜(AFM)研究纳米雄黄与SUV仿生膜的相互作用,证实了磷脂是纳米雄黄作用的关键靶分子.随纳米雄黄结合,SUV仿生膜的相对粘度聃值增大,膜的流动性减小.Raman光谱数据计算表明,作用后膜的纵向有序性参数s。。及横向有序性参数Slat值增大,说明纳米雄黄的结合使磷脂膜的脂酰基链全反式构型比例上升,膜的流动性减小.由Raman光谱和引PNMR结果推测,磷脂极性头部是纳米雄黄与磷脂的主要结合位点。AFM实时观测,纳米雄黄通过在膜表面打“孔”或“洞”的方式,损坏磷脂膜. 相似文献
11.
The liposome of small unilamellar vesicles (SUV) made from phosphatidylcholine-cholesterol mixtures was used as a simple model for biomimetic membranes. The studies on the interaction between the liposome and realgar nanoparticles (NPs) demonstrate that the phospholipid is one of the key targeted molecules of realgar NPs, used by surface plasmon resonance (SPR) technology, fluorescence polarization, Raman spectroscopy, nuclear magnetic resonance (NMR) and atom force microscope (AFM). It was observed that th... 相似文献
12.
Dielectric monitoring of the adsorption or release process of salicylic acid (SA) by chitosan membrane shows that the dielectric spectra of the chitosan membrane/ SA solution systems change regularly in the adsorption or release process. By analyzing the regularity, a new mechanism for the relaxations is proposed. The concentration polarization layer (CPL) caused by SA adsorption or release is confirmed to be essential for the dielectric relaxations. The changes of the spectra with time are explained by account of the relationship between CPL properties and dielectric strength. Based on this relaxation mechanism, a theoretical method can be established to calculate dynamical parameters of inner structure of the adsorption or release systems from their dielectric spectra. Therefore, dielectric spec- troscopy is demonstrated to be a promising method for estimating interfacial distribution of ionic sub- stances and their binding to membrane in a non-invasive way. 相似文献
13.
Molecular dynamics simulation on the interaction between polymer inhibitors and anhydrite surface
下载免费PDF全文
![点击此处可从《Surface and interface analysis : SIA》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Jian‐Ping Zeng Yong Dai Wen‐Yan Shi Jing‐Ling Shao Guo‐Xiang Sun 《Surface and interface analysis : SIA》2015,47(9):896-902
Investigation on the microscopic interaction between polymer inhibitors and calcium sulfate will be helpful for understanding its scale inhibition mechanism and can provide a theoretical guidance to developing new scale inhibitors. In this work, molecular dynamics simulations with COMPASS force field have been performed to simulate the interaction between hydrolyzed polymaleic anhydride (HPMA), polyaspartic acid (PASP), polyepoxysuccinic acid (PESA), polyacrylic acid (PAA) and the (001) and (020) surfaces of anhydrite (AD) crystal with and without water. The results show that the sequence of binding energies between four polymer inhibitors and AD (001) and (020) with water is PESA > PASP > HPMA > PAA. The binding energy of the same polymer inhibitor on AD (001) is smaller than that on AD (020). Water molecules weaken the deformations of HPMA and PAA but aggravate those of PASP and PESA. Natural bond orbital (NBO) charges of the repeat units of polymer inhibitors were calculated by B3LYP/6‐31G* method. The Coulomb interaction is formed between the O atoms of polymer inhibitors and the Ca atoms of AD crystal. The system of polymer–AD is mainly contributed from the non‐bonding interaction. Polymer inhibitors do not interact directly with AD crystal, but indirectly through the interactions between inhibitor–H2O and H2O–AD, i.e. water molecules participate in scale inhibition of polymer inhibitors to AD crystal. Water molecules cannot be ignored when the interaction models are constructed, i.e. solvent effect cannot be ignored. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
14.
Hong-Xiang Zhao Bao-Huai Wang You-Min Zhang 《Journal of Thermal Analysis and Calorimetry》1995,45(1-2):27-33
The thermal curves and the enthalpy changes of the interaction between some oral sustained release preparations (Contac, Fenbid and Benza sustained release capsules) and physiological saline have been measured at 298.15 K with a MS-80 standard Calvet microcalorimeter. The curves that recorded the changes of heat effect with time have clearly shown the sustained release action and process of the above preparations. A method for examining the sustained release action of sustained release preparations can be developed from the above experiments. The principle of application and the experimental procedure of this method have been expounded, and some results of the above experiments have also been discussed. 相似文献
15.
Gaitzsch J Appelhans D Gräfe D Schwille P Voit B 《Chemical communications (Cambridge, England)》2011,47(12):3466-3468
Crosslinkable and pH-sensitive amphiphilic block copolymers are promising candidates to establish pH-stable and permeable vesicles for synthetic biology. Here, we report the fabrication of crosslinked and pH-stable polymersomes as swellable vesicles for the pH-dependent loading and release of small dye molecules. 相似文献
16.
Jörg Votteler Elena Iavnilovitch Orit Fingrut Vivian Shemesh Daniel Taglicht Omri Erez Stefan Sörgel Torsten Walther Norbert Bannert Ulrich Schubert Yuval Reiss 《BMC biochemistry》2009,10(1):1-14
Background
The ALG2-interacting protein X (ALIX)/AIP1 is an adaptor protein with multiple functions in intracellular protein trafficking that plays a central role in the biogenesis of enveloped viruses. The ubiquitin E3-ligase POSH (plenty of SH3) augments HIV-1 egress by facilitating the transport of Gag to the cell membrane. Recently, it was reported, that POSH interacts with ALIX and thereby enhances ALIX mediated phenotypes in Drosophila.Results
In this study we identified ALIX as a POSH ubiquitination substrate in human cells: POSH induces the ubiquitination of ALIX that is modified on several lysine residues in vivo and in vitro. This ubiquitination does not destabilize ALIX, suggesting a regulatory function. As it is well established that ALIX rescues virus release of L-domain mutant HIV-1, HIV-1ΔPTAP, we demonstrated that wild type POSH, but not an ubiquitination inactive RING finger mutant (POSHV14A), substantially enhances ALIX-mediated release of infectious virions derived from HIV-1ΔPTAP L-domain mutant (YPXnL-dependent HIV-1). In further agreement with the idea of a cooperative function of POSH and ALIX, mutating the YPXnL-ALIX binding site in Gag completely abrogated augmentation of virus release by overexpression of POSH. However, the effect of the POSH-mediated ubiquitination appears to be auxiliary, but not necessary, as silencing of POSH by RNAi does not disturb ALIX-augmentation of virus release.Conclusion
Thus, the cumulative results identified ALIX as an ubiquitination substrate of POSH and indicate that POSH and ALIX cooperate to facilitate efficient virus release. However, while ALIX is obligatory for the release of YPXnL-dependent HIV-1, POSH, albeit rate-limiting, may be functionally interchangeable. 相似文献17.
Molecular dynamics investigation of the interaction between IR radiation and an ammonia-water medium
A. E. Galashev 《Russian Journal of Physical Chemistry A, Focus on Chemistry》2013,87(6):963-966
The frequency dependence of the absorption factor and refractive index of a dispersion water system absorbing ammonia are studied by means of molecular dynamics. It is found that the capture of the ammonia molecules by water clusters is accompanied by a substantial reduction in their ability to absorb IR radiation in the frequency range 0 ≤ ω ≤ 3500 cm?1, and the refractive index of the ammonia-water system of clusters is lowered. It is shown that the maxima of the absorption spectra and the refractive index shift to higher frequencies. Starting from a certain concentration of ammonia in the clusters, however, the integral intensity of the spectra increases. 相似文献
18.
We calculated the potential of mean force (PMF) for the interaction between a model zwitterionic bilayer and a model charged bilayer. To understand the role of water, we separated the PMF into two components: one due to direct interaction and the other due to water-mediated interaction. In our calculations, we observed that water-mediated interaction is attractive at larger distances and repulsive at shorter. The calculation of the entropic and enthalpic contributions to the solvent-mediated components of the PMF showed that attraction is entropically dominant, while repulsion is dominated by the enthalpy. 相似文献
19.
20.
Bill X. Huang Hee-Yong Kim 《Journal of the American Society for Mass Spectrometry》2009,20(8):1504-1513
The serine/threonine kinase Akt is a critical enzyme that regulates cell survival. As high Akt activity has been shown to
contribute to the pathogenesis of various human malignancies, inhibition of Akt activation is a promising therapeutic strategy
for cancers. We have previously demonstrated that changes in Akt interdomain arrangements from a closed to open conformation
occur upon Akt-membrane interaction, which in turn allows Akt phosphorylation/activation. In the present study, we demonstrate
a novel strategy to discern mechanisms for Akt inhibition based on Akt conformational changes using chemical cross-linking
and 18O labeling mass spectrometry. By quantitative comparison of two interdomain cross-linked peptides, which represent the proximity
of the domains involved, we found that the binding of Akt to an inhibitor (PI analog) caused the open interdomain conformation
where the PH and regulatory domains moved away from the kinase domain, even before interacting with membranes, subsequently
preventing translocation of Akt to the plasma membrane. In contrast, the interdomain conformation remained unchanged after
incubating with another type of inhibitor (peptide TCL1). Subsequent interaction with unilamellar vesicles suggested that
TCL1 impaired particularly the opening of the PH domain for exposing T308 for phosphorylation at the plasma membrane. This
novel approach based on the conformation-based molecular interaction mechanism should be potentially useful for drug discovery
efforts for specific Akt inhibitors or anti-tumor agents. 相似文献