The Experts below are selected from a list of 2415 Experts worldwide ranked by ideXlab platform
Stephen G. Weber - One of the best experts on this subject based on the ideXlab platform.
-
Effect of polymer concentration on partitioning and molecular recognition in plasticized poly(vinyl chloride).
Analytical Chemistry, 2003Co-Authors: Xu Zhang, Raymond Nims, Hong Zhao, Zhi Chen, Stephen G. WeberAbstract:Mixtures of poly(vinyl chloride) (PVC) with plasticizers have been used in ion-selective electrodes for many years. The same material has proven useful in solid-phase microextraction (SPME), both with and without Artificial Receptors. We hypothesized that by changing the polymer concentration in plasticized PVC membranes containing Artificial Receptor from the standard 33 wt %, the selectivity of the extraction of barbiturates over similar molecules could be improved. Partition coefficients and Receptor−substrate formation constants of a target species, phenobarbital, in membranes with various polymer concentrations were determined. Diffusion coefficients of the solute phenobarbital in Receptor-free membranes were also determined. Kamlet−Taft solvatochromic properties β and π* were measured for the PVC/dioctyl sebacate materials. Cohesive energy densities were calculated for the same materials. Partition coefficients for phenobarbital (from aqueous solution to membrane) decrease as [PVC] increases, while ...
-
steady state concentration distribution of Artificial Receptor and target analyte in plasticized pvc membrane between solutions differing in target analyte concentration
Analytical Chemistry, 2002Co-Authors: Xu Zhang, Hong Zhao, Stephen G. WeberAbstract:A barbiturate Receptor has proven effective in improving selectivity in solid-phase microextraction of barbiturates when doped into plasticized poly(vinyl chloride) (PVC). It would be beneficial to have selective extractions for any given organic species; however, the Receptors do not exist. They will be found by screening of libraries of potential Receptors; thus, a screening method is needed. It is important to screen the Receptors in the medium in which they will work: plasticized PVC. We hypothesize that we can make Receptors move in solution in response to the presence of a solute to which they bind. This work examines whether we can establish a sufficient free energy gradient for a good Receptor to move to a predetermined place in space. A difference in the barbiturate solute (substrate or guest) concentration in solutions bathing the two sides of a plasticized PVC membrane containing the barbiturate Receptor (or host) creates a spatial concentration gradient of the substrate in the membrane. This causes the Receptor's chemical potential to vary across the membrane. Upon binding to the analyte, the Receptor undergoes a local activity drop, which decreases its free energy. This process produces a flux of Receptor to accumulate at place where there is a high substrate concentration. A concentration gradient of substrate can be maintained across the membrane at steady state. In membranes for which the formation of the complex is favored, the Receptor responds to the gradient of substrate. In membranes for which binding is not favored, a gradient of substrate is completely ignored by the Receptor. Thus, the Receptor does respond to the gradient but only if the concentration gradient of guest corresponds to a chemical potential gradient.
-
Enhanced Extraction of Phenobarbital from Serum with a Designed Artificial Receptor
Analytical chemistry, 1994Co-Authors: Jane N. Valenta, Andrew D. Hamilton, Robert P. Dixon, Stephen G. WeberAbstract:The primary goal of this work was to determine whether Artificial Receptors that function on the basis of molecular recognition have analytical capabilities. As an example of such a Receptor, we have chosen one directed toward barbiturates. Chloroform enriched with this Artificial Receptor (1 mM) can extract more than 90% of the phenobarbital from a 20 microM phenobarbital solution in human control serum using a volume ratio (organic/serum) as small as 0.5. In the absence of this Receptor, the volume ratio must be greater than 10 to achieve similar extraction efficiencies. In addition to volume ratio, the role of pH, Receptor concentration, and solvent type are discussed. The experimental results are found to be in good agreement with predictions based on chemical equilibria. Through the use of this and other similar Receptors, the amount of organic solvent used in extractions can be minimized.
Itaru Hamachi - One of the best experts on this subject based on the ideXlab platform.
-
Coupling a natural Receptor protein with an Artificial Receptor to afford a semisynthetic fluorescent biosensor.
Journal of the American Chemical Society, 2004Co-Authors: Eiji Nakata, Seiji Shinkai, Tsuyoshi Nagase, Itaru HamachiAbstract:An Artificial Receptor and a signal transducer have been engineered on a lectin (saccharide-binding protein) surface by a post-photoaffinity labeling modification method. Saccharide binding can be directly and selectively read out by the fluorescence changes of the fluorophore via photoinduced electron transfer (PET) mode. Fluorescence titration with various saccharides reveals that molecular recognition by the Artificial Receptor is successfully coupled to the native binding site of the lectin, producing a novel fluorescent saccharide biosensor showing modulated specificity and enhanced affinity. Designed cooperativity between Artificial and native molecular recognition modules was quantitatively demonstrated by the comparison of the binding affinities, and it represents a new strategy in molecular recognition. By using appropriate Artificial Receptors and various native lectins, this approach may provide many new semisynthetic biosensors for saccharide derivatives such as glycolipids and glycopeptides/proteins. An extended library of lectin-based biosensors is envisioned to be useful for glycome research, a newly emerging field of the post-genomic era.
-
cross linking strategy for molecular recognition and fluorescent sensing of a multi phosphorylated peptide in aqueous solution
Journal of the American Chemical Society, 2003Co-Authors: Akio Ojida, Masa Aki Inoue, Yasuko Mitooka, Itaru HamachiAbstract:In the research field of molecular recognition, selective recognition and sensing of phosphorylated protein surfaces is strongly desirable both for elucidation of protein−protein recognition at the molecular level and for regulation of signal transduction through protein surfaces. Here we describe a new strategy for molecular recognition of a multi-phosphorylated peptide using intrapeptide cross-linking on the basis of coordination chemistry. The present Artificial Receptor can selectively bind to doubly phosphorylated peptide through multiple-point interactions and fluorescently sense the binding event with an association constant of more than 106 M-1 in neutral aqueous solution.
-
Zn(II) dipicolylamine-based Artificial Receptor as a new entry for surface recognition of α-helical peptides in aqueous solution
Tetrahedron Letters, 2001Co-Authors: Yasuko Mito-oka, Shinya Tsukiji, Noriyuki Kasagi, Takashi Hiraoka, Seiji Shinkai, Itaru HamachiAbstract:Abstract It is clear by CD spectral titration that Zn(II)dipicolylamine-based dinuclear complexes selectively bind and stabilize the α-helix conformation of peptides having two histidine (His) residues at specific positions ( H-i and i +4 or i +7 or i +11).
Christian J. Buchholz - One of the best experts on this subject based on the ideXlab platform.
-
the Receptor attachment function of measles virus hemagglutinin can be replaced with an autonomous protein that binds her2 neu while maintaining its fusion helper function
Journal of Virology, 2013Co-Authors: Anke Rasbach, Tobias Abel, Robert C. Münch, Klaus Boller, Jurgen Schneiderschaulies, Christian J. BuchholzAbstract:Cell entry of enveloped viruses is initiated by attachment to the virus Receptor followed by fusion between the virus and host cell membranes. Measles virus (MV) attachment to its Receptor is mediated by the hemagglutinin (H), which is thought to produce conformational changes in the membrane fusion protein (F) that trigger insertion of its fusion peptide into the target cell membrane. Here, we uncoupled Receptor attachment and the fusion-helper function of H by introducing Y481A, R533A, S548L, and F549S mutations into the viral attachment protein that made it blind to its normal Receptors. An Artificial Receptor attachment protein specific for Her2/neu was incorporated into the membranes of pseudotyped lentivirus particles as a separate transmembrane protein along with the F protein. Surprisingly, these particles entered efficiently into Her2/neu-positive SK-OV-3 as well as CHO-Her2 cells. Cell entry was independent of endocytosis but strictly dependent on the presence of H. H-specific monoclonal antibodies, as well as a mutation in H interfering with H/F cooperation, blocked cell entry. The particles mediated stable and specific transfer of reporter genes into Her2/neu-positive human tumor cells also in vivo, while exhibiting improved infectivity and higher titers than Her2/neu-targeted vectors displaying the targeting domain on H. Extending the current model of MV cell entry, the data suggest that Receptor binding of H is not required for its fusion-helper function but that particle-cell contact in general may be sufficient to induce the conformational changes in the H/F complex and activate membrane fusion.
-
The Receptor Attachment Function of Measles Virus Hemagglutinin Can Be Replaced with an Autonomous Protein That Binds Her2/neu While Maintaining Its Fusion-Helper Function
Journal of Virology, 2013Co-Authors: Anke Rasbach, Tobias Abel, Robert C. Münch, Klaus Boller, Jürgen Schneider-schaulies, Christian J. BuchholzAbstract:Cell entry of enveloped viruses is initiated by attachment to the virus Receptor followed by fusion between the virus and host cell membranes. Measles virus (MV) attachment to its Receptor is mediated by the hemagglutinin (H), which is thought to produce conformational changes in the membrane fusion protein (F) that trigger insertion of its fusion peptide into the target cell membrane. Here, we uncoupled Receptor attachment and the fusion-helper function of H by introducing Y481A, R533A, S548L, and F549S mutations into the viral attachment protein that made it blind to its normal Receptors. An Artificial Receptor attachment protein specific for Her2/neu was incorporated into the membranes of pseudotyped lentivirus particles as a separate transmembrane protein along with the F protein. Surprisingly, these particles entered efficiently into Her2/neu-positive SK-OV-3 as well as CHO-Her2 cells. Cell entry was independent of endocytosis but strictly dependent on the presence of H. H-specific monoclonal antibodies, as well as a mutation in H interfering with H/F cooperation, blocked cell entry. The particles mediated stable and specific transfer of reporter genes into Her2/neu-positive human tumor cells also in vivo, while exhibiting improved infectivity and higher titers than Her2/neu-targeted vectors displaying the targeting domain on H. Extending the current model of MV cell entry, the data suggest that Receptor binding of H is not required for its fusion-helper function but that particle-cell contact in general may be sufficient to induce the conformational changes in the H/F complex and activate membrane fusion.
Frankgerrit Klarner - One of the best experts on this subject based on the ideXlab platform.
-
molecular tweezers for lysine and arginine powerful inhibitors of pathologic protein aggregation
Chemical Communications, 2016Co-Authors: Thomas Schrader, Gal Bitan, Frankgerrit KlarnerAbstract:Molecular tweezers represent the first class of Artificial Receptor molecules that have made the way from a supramolecular host to a drug candidate with promising results in animal tests. Due to their unique structure, only lysine and arginine are well complexed with exquisite selectivity by a threading mechanism, which unites electrostatic, hydrophobic and dispersive attraction. However, tweezer design must avoid self-dimerization, self-inclusion and external guest binding. Moderate affinities of molecular tweezers towards sterically well accessible basic amino acids with fast on and off rates protect normal proteins from potential interference with their biological function. However, the early stages of abnormal Aβ, α-synuclein, and TTR assembly are redirected upon tweezer binding towards the generation of amorphous non-toxic materials that can be degraded by the intracellular and extracellular clearance mechanisms. Thus, specific host–guest chemistry between aggregation-prone proteins and lysine/arginine binders rescues cell viability and restores animal health in models of AD, PD, and TTR amyloidosis.
-
A Molecular Tweezer for Lysine and Arginine
Journal of the American Chemical Society, 2005Co-Authors: Michael Fokkens, Thomas Schrader, Frankgerrit KlarnerAbstract:Lysine and arginine play a key role in numerous biological recognition processes controlling, inter alia, gene regulation, glycoprotein targeting and vesicle transport. They are also found in signaling peptide sequences responsible, e.g. for bacterial cell wall biosynthesis, Alzheimer peptide aggregation and skin regeneration. Almost none of all Artificial Receptor structures reported to date are selective and efficient for lysine residues in peptides or proteins. An Artificial molecular tweezer is introduced which displays an exceptionally high affinity for lysine (Ka ≈ 5000 in neutral phosphate buffer). It features an electron-rich torus-shaped cavity adorned with two peripheral anionic phosphonate groups. Exquisite selectivity for arginine and lysine is achieved by threading the whole amino acid side chain through the cavity and subsequent locking by formation of a phosphonate−ammonium/guanidinium salt bridge. This pseudorotaxane-like geometry is also formed in small basic signaling peptides, which can...
Xiaolei Zuo - One of the best experts on this subject based on the ideXlab platform.
-
rapid transmembrane transport of dna nanostructures by chemically anchoring Artificial Receptors on cell membranes
ChemPlusChem, 2019Co-Authors: Jiangbo Liu, Mengying Deng, Noshin Afshan, Xiaolei ZuoAbstract:Highly efficient transmembrane transport of exogenous reagents into cells is of vital importance for developing drug-delivery systems. Conventionally, transmembrane transport of exogenous reagents was accomplished with the assistance of transfection agents or other Artificial means. However, the high toxicity and low transport efficiency of current delivery techniques still remain to be solved. In this work, by anchoring Artificial Receptors onto cell membranes with a mild chemical reaction, we demonstrated that the exogenous reagent framework nucleic acids, namely tetrahedral DNA nanostructures (TDN) can bind onto cell membranes effectively by the hybridization between single-stranded DNA (ssDNA) and pendant ssDNA of TDN. The transport rate was greatly enhanced, with the endocytosis time could be as fast as 0.5 h. Furthermore, the transport quantity was prominently improved, with around 30 % of TDN endocytosed within 4 h. Owing to its rapid transmembrane transport speed and improved endocytosis quantity, this Artificial-Receptor-mediated transmembrane transport is a promising tool for achieving rapid and highly efficient transmembrane transport of exogenous reagents.
