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12270611
Common solubilizers to estimate the Caco-2 transport of poorly water-soluble drugs.
Solubilizers are often used to enhance the bioavailability of drugs with poor aqueous solubility. This study focuses on the use of the Caco-2 system containing solubilizers to predict the absorption of poorly water-soluble drugs in humans. First, the effects of propylene glycol (PG), hydroxypropyl-beta-cyclodextrin (HP...
12270606
The effects of water-soluble cyclodextrins on the histological integrity of the rat nasal mucosa.
The aim of this study was to investigate the effect of highly water-soluble cyclodextrins (CDs) on the histological integrity of the nasal mucosa. In order to evaluate their effects, the in vivo single and repeated nasal exposure studies were performed using male Wistar rats. The rat nasal cavity was excised after an a...
12270193
1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 4: synthesis of N-1 acidic functionality affording analogues with enhanced antiviral activity against HIV.
A series of alpha-(pyrrolidin-1-yl)acetic acids is presented as selective and potent antivirals against HIV. Several of the pyrrolidine zwitterions demonstrated reasonable in vitro properties, enhanced antiviral activities and improved pharmacokinetic profiles over pyrrolidine 1.
12269795
Structural biology of viruses by the combination of electron cryomicroscopy and X-ray crystallography.
Recent developments in electron cryomicroscopy and image analysis have made it a powerful tool to investigate the structure, assembly, and dynamics of biological supramolecular assemblies. The subjects of study now include a variety of biological samples that may be homogeneous or heterogeneous, symmetric or nonsymmetr...
12242295
Structural basis for activation of fibroblast growth factor signaling by sucrose octasulfate.
Sucrose octasulfate (SOS) is believed to stimulate fibroblast growth factor (FGF) signaling by binding and stabilizing FGFs. In this report, we show that SOS induces FGF-dependent dimerization of FGF receptors (FGFRs). The crystal structure of the dimeric FGF2-FGFR1-SOS complex at 2.6-A resolution reveals a symmetric a...
12241997
CNS activities of liquid and spray-dried extracts from Lippia alba-Verbenaceae (Brazilian false melissa).
The CNS activity of Lippia alba liquid and spray-dried extracts, containing the non-volatile fraction from the leaves, was investigated. L. alba liquid extracts were prepared by percolation with EtOH 40, 60 or 80%. The liquid extracts, named ES(40%,) ES(60%) and ES(80%,) were concentrated, the ethanol eliminated and th...
12239334
Protective antiviral immune responses to pseudorabies virus induced by DNA vaccination using dimethyldioctadecylammonium bromide as an adjuvant.
To enhance the efficacy of a DNA vaccine against pseudorabies virus (PRV), we evaluated the adjuvant properties of plasmids coding for gamma interferon or interleukin-12, of CpG immunostimulatory motifs, and of the conventional adjuvants dimethyldioctadecylammonium bromide in water (DDA) and sulfolipo-cyclodextrin in s...
12239329
Specificity and affinity of sialic acid binding by the rhesus rotavirus VP8* core.
Nuclear magnetic resonance spectroscopy demonstrates that the rhesus rotavirus hemagglutinin specifically binds alpha-anomeric N-acetylneuraminic acid with a K(d) of 1.2 mM. The hemagglutinin requires no additional carbohydrate moieties for binding, does not distinguish 3' from 6' sialyllactose, and has approximately t...
12239322
Influenza virus can enter and infect cells in the absence of clathrin-mediated endocytosis.
Influenza virus has been described to enter host cells via clathrin-mediated endocytosis. However, it has also been suggested that other endocytic routes may provide additional entry pathways. Here we show that influenza virus may enter and infect HeLa cells that are unable to take up ligands by clathrin-mediated endoc...
12239318
Selective translation of eukaryotic mRNAs: functional molecular analysis of GRSF-1, a positive regulator of influenza virus protein synthesis.
To understand the regulation of cap-dependent translation initiation mediated by specific 5' untranslated region (UTR) RNA-protein interactions in mammalian cells, we have studied the selective translation of influenza virus mRNAs. Previous work has shown that the host cell mRNA binding protein guanine-rich sequence fa...
12239312
Role for human immunodeficiency virus type 1 membrane cholesterol in viral internalization.
The membrane of human immunodeficiency virus type 1 (HIV-1) virions contains high levels of cholesterol and sphingomyelin, an enrichment that is explained by the preferential budding of the virus through raft microdomains of the plasma membrane. Upon depletion of cholesterol from HIV-1 virions with methyl-beta-cyclodex...
12239308
Functional dissection of latency-associated nuclear antigen 1 of Kaposi's sarcoma-associated herpesvirus involved in latent DNA replication and transcription of terminal repeats of the viral genome.
Latency-associated nuclear antigen 1 (LANA1) of Kaposi's sarcoma-associated herpesvirus (KSHV) is implicated in the maintenance of the viral genome during latent infection. LANA1 colocalizes with KSHV episomes on the host chromosome and mediates their maintenance by attaching these viral structures to host chromosomes....
12239302
Mimovirus: a novel form of vaccine that induces hepatitis B virus-specific cytotoxic T-lymphocyte responses in vivo.
CD8(+) cytotoxic T lymphocytes (CTLs) are now recognized as important mediators of immunity against intracellular pathogens, including human immunodeficiency virus and tumors. How to efficiently evoke antigen-specific CTL responses in vivo has become a crucial problem in the development of modern vaccines. Here, we dev...
12239290
Magnitude and frequency of cytotoxic T-lymphocyte responses: identification of immunodominant regions of human immunodeficiency virus type 1 subtype C.
A systematic analysis of immune responses on a population level is critical for a human immunodeficiency virus type 1 (HIV-1) vaccine design. Our studies in Botswana on (i) molecular analysis of the HIV-1 subtype C (HIV-1C) epidemic, (ii) frequencies of major histocompatibility complex class I HLA types, and (iii) cyto...
12237470
Mapping and characterization of the functional epitopes of tissue inhibitor of metalloproteinases (TIMP)-3 using TIMP-1 as the scaffold: a new frontier in TIMP engineering.
Tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE/ADAM-17) is responsible for the release of TNF-alpha, a potent proinflammatory cytokine associated with many chronic debilitating diseases such as rheumatoid arthritis. Among the four variants of mammalian tissue inhibitor of metalloproteinases (TIMP-1 to ...
12237456
Molecular dynamics simulations of alanine rich beta-sheet oligomers: Insight into amyloid formation.
The aggregation observed in protein conformational diseases is the outcome of significant new beta-sheet structure not present in the native state. Peptide model systems have been useful in studies of fibril aggregate formation. Experimentally, it was found that a short peptide AGAAAAGA is one of the most highly amyloi...
12234834
Biochemical and genetic characterization of the vanC-2 vancomycin resistance gene cluster of Enterococcus casseliflavus ATCC 25788.
The vanC-2 cluster of Enterococcus casseliflavus ATCC 25788 consisted of five genes (vanC-2, vanXY(C-2), vanT(C-2), vanR(C-2), and vanS(C-2)) and shared the same organization as the vanC cluster of E. gallinarum BM4174. The proteins encoded by these genes displayed a high degree of amino acid identity to the proteins e...
12231356
Integrin-associated proteins.
A diverse group of plasma membrane proteins have been found associated with integrins in supramolecular complexes. These associated plasma membrane molecules can modulate virtually all integrin functions by altering signal transduction arising from integrin ligation. In the past two years, new examples of signaling thr...
12228313
Cellular localization of Babesia bovis merozoite rhoptry-associated protein 1 and its erythrocyte-binding activity.
The cellular localization of Babesia bovis rhoptry-associated protein 1 (RAP-1) and its erythrocyte-binding affinity were examined with anti-RAP-1 antibodies. In an indirect immunofluorescent antibody test, RAP-1 was detectable in all developmental stages of merozoites and in extracellular merozoites. In the early stag...
12228263
BhuR, a virulence-associated outer membrane protein of Bordetella avium, is required for the acquisition of iron from heme and hemoproteins.
Iron (Fe) is an essential element for most organisms which must be obtained from the local environment. In the case of pathogenic bacteria, this fundamental element must be acquired from the fluids and tissues of the infected host. A variety of systems have evolved in bacteria for efficient acquisition of host-bound Fe...
12226848
Cyclodextrin complexes of sulfonamide carbonic anhydrase inhibitors as long-lasting topically acting antiglaucoma agents.
Complexes of several 1,3,4-thiadiazole-2-sulfonamide derivatives possessing strong carbonic anhydrase (CA) inhibitory properties with beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin were obtained and characterized. Although the investigated CA inhibitors possessed very powerful inhibitory properties against the t...
12217197
Transgenic IL-2 expression in Ewing tumor cell lines after transfection with Starburst dendrimers and cationic liposomes.
Immunotherapy with IL-2-transduced cells requires efficient methods of gene transfer. Nonviral methods have been studied intensively in recent years. This study examined whether tumor and fibroblast cell lines established from Ewing tumor patients could be efficiently transfected with the IL-2 gene. Starburst dendrimer...
12215539
Gene structure and functional analysis of the mouse nidogen-2 gene: nidogen-2 is not essential for basement membrane formation in mice.
Nidogens are highly conserved proteins in vertebrates and invertebrates and are found in almost all basement membranes. According to the classical hypothesis of basement membrane organization, nidogens connect the laminin and collagen IV networks, so stabilizing the basement membrane, and integrate other proteins. In m...
12208986
A hepatitis B surface antigen mutant that lacks the antigenic loop region can self-assemble and interact with the large hepatitis delta antigen.
A novel hepatitis B virus surface antigen mutant harboring a deletion of most of the major antigenic loop region was competent for self-assembly and secretion. Although the mutant protein was competent for interaction with and incorporation of free large hepatitis delta antigen, it was partially defective in hepatitis ...
12208966
Mutagenic stabilization and/or disruption of a CD4-bound state reveals distinct conformations of the human immunodeficiency virus type 1 gp120 envelope glycoprotein.
The human immunodeficiency virus type 1 (HIV-1) gp120 exterior envelope glycoprotein is conformationally flexible. Upon binding to the host cell receptor CD4, gp120 assumes a conformation that is recognized by the second receptor, CCR5 and/or CXCR4, and by the CD4-induced (CD4i) antibodies. Guided by the X-ray crystal ...
12209468
Sequence-specific recognition of DNA by hydrophobic, alanine-rich mutants of the basic region/leucine zipper motif investigated by fluorescence anisotropy.
We generated minimalist proteins capable of sequence-specific, high-affinity binding of DNA to probe how proteins are used and can be used to recognize DNA. In order to quantify binding affinities and specificities in our protein-DNA system, we used fluorescence anisotropy to measure in situ the thermodynamics of bindi...
12182305
Fibroblast adhesion and proliferation on poly(ethylene glycol) hydrogels crosslinked by hydrolyzable polyrotaxane.
Fibroblast culture was performed to evaluate cell adhesion and proliferation on poly(ethylene glycol) (PEG) hydrogels crosslinked by a hydrolyzable polyrotaxane. The polyrotaxane consisting of alpha-cyclodextrins (alpha-CDs) and PEG terminated by benzyloxycarbonyl (Z)-L-phenylalanine (L-Phe) via ester linkage was used ...
12150875
Cocaine detoxification by combinatorially substituted beta-cyclodextrin libraries.
Per-6-substituted- and A,C,E(F)-tri-6-substituted-6-deoxy-beta-cyclodextrin (beta-CD) libraries were generated using solution-phase combinatorial chemistry techniques starting from the corresponding iodo precursors and different combinations of individual amine nucleophiles. Using a high throughput electrospray mass sp...
12357034
Crystal structure of human calcineurin complexed with cyclosporin A and human cyclophilin.
Calcineurin (Cn), a Ca(2+)/calmodulin-dependent Ser/Thr protein phosphatase, is an important participant in signaling pathways that activate T cells. It is the target of the immunosuppressive drugs cyclosporin A (CsA) and FK506. These drugs bind proteins known as cyclophilin (Cyp) and FK506-binding protein, respectivel...
12357033
Solution structure and dynamics of the outer membrane enzyme PagP by NMR.
The bacterial outer membrane enzyme PagP transfers a palmitate chain from a phospholipid to lipid A. In a number of pathogenic Gram-negative bacteria, PagP confers resistance to certain cationic antimicrobial peptides produced during the host innate immune response. The global fold of Escherichia coli PagP was determin...
12359931
Transition metal complexes with thiosemicarbazide-based ligands. XLIV. Aqua(3-hydroxy-5-hydroxymethyl-2-methylpyridine-4-carboxaldehyde 3-methylisothiosemicarbazone-kappa(3)O,N1,N4)nitratocopper(II) nitrate.
Part XLIII: Novaković et al. (2002). The title complex, [Cu(NO(3))(C(10)H(14)N(4)O(2)S)(H(2)O)](NO(3)), is the first metal complex with a Schiff base derived from isothiosemicarbazide and pyridoxal (pyridoxal is 3-hydroxy-5-hydroxymethyl-2-methylpyridine-4-carboxaldehyde). The Cu(II) environment is a square pyramid, th...
12350233
Binding of the baculovirus very late expression factor 1 (VLF-1) to different DNA structures.
<h4>Background</h4>Baculovirus genomes encode a gene called very late expression factor 1 (VLF-1) that is a member of the integrase (Int) family of proteins. In this report we describe the binding properties of purified Autographa californica multiple capsid nucleopolyhedrovirus (AcMNPV) VLF-1 to a number of different ...
12354766
Biglycan organizes collagen VI into hexagonal-like networks resembling tissue structures.
The ability of the leucine-rich repeat (LRR) proteins biglycan, decorin, and chondroadherin to interact with collagen VI and influence its assembly to supramolecular structures was studied by electron microscopy and surface plasmon resonance measurements in the BIAcore 2000 system. Biglycan showed a unique ability to o...
12351646
Biochemical characterization of CopA, the Escherichia coli Cu(I)-translocating P-type ATPase.
Escherichia coli CopA is a copper ion-translocating P-type ATPase that confers copper resistance. CopA formed a phosphorylated intermediate with [gamma-(32)P]ATP. Phosphorylation was inhibited by vanadate and sensitive to KOH and hydroxylamine, consistent with acylphosphate formation on conserved Asp-523. Phosphorylati...
12324702
Some errors from the crystallographic literature, some amplifications and a questionable result.
The space groups of [[Mo(2)(O(2)CCH(3))(4)('linker')](n)] are corrected from P1 to C2/m for 'linker' = pyrazine and 1,4-diazabicyclo[2.2.2]octane (dabco) and from P1 to C2/c for 'linker' = 4,4'-bipyridine. Also, [[tris-(2-pyridylmethyl)amine]BrV(mu-O)VBr[tris-(2-pyridylmethyl)amine]]Br.H(2)O is corrected from P1 to C2/...
12324698
An exceptionally stable peptide nanotube system with flexible pores.
The hydrophobic channels in the structure of the dipeptide L-alanyl-L-valine act as supramolecular hosts for organic solvent molecules. In a series of data collections, it is demonstrated that small molecules like acetonitrile, methanol and acetone can be removed from the channels by drying without impairing the struct...
12324691
Ferrocene-1,1'-dicarboxylic acid as a building block in supramolecular chemistry: supramolecular structures in one, two and three dimensions.
The supramolecular structures have been determined for nine adducts formed between organic diamines and ferrocene-1,1'-dicarboxylic acid. In the salt-like 1:1 adduct (1) formed with methylamine, the supramolecular structure is one-dimensional, whereas in the 1:1 adducts formed with 1,4-diazabicyclo[2.2.2]octane, (2), a...
12271131
Galectin-1 is a stromal cell ligand of the pre-B cell receptor (BCR) implicated in synapse formation between pre-B and stromal cells and in pre-BCR triggering.
Although preB cell-receptor (pre-BCR) formation and cell-surface expression is essential for B cell development, pre-BCR generation of signal transduction remains elusive. Here, we report that recombinant pre-BCRs and the surrogate light chain bind specifically to the bone marrow stromal cell galectin-1 (GAL1), an S-ty...
12352968
Molecular anatomy of antigen-specific CD8(+) T cell engagement and synapse formation in vivo.
Antigen-specific CD8(+) T cells are required for the clearance of most viral infections and several cancers. However, it is not clear in vivo whether CD8(+) T cells can engage multiple targets simultaneously, engagement results in the formation of an immunologic synapse or molecules involved in CD8 function are redistr...
12244093
On the binding preference of human groups IIA and X phospholipases A2 for membranes with anionic phospholipids.
Mammals contain 9-10 secreted phospholipases A(2) (sPLA(2)s) that display widely different affinities for membranes, depending on the phospholipid composition. The much higher enzymatic activity of human group X sPLA(2) (hGX) compared with human group IIA sPLA(2) (hGIIA) on phosphatidylcholine (PC)-rich vesicles is due...
12397506
The supramolecular structure of ultrafiltration membranes synthesized by electropolymerization.
The structure and morphology of polyacrylamide-formaldehyde ultrafiltration membranes synthesized by electropolymerization of monomers have been investigated by scanning electron microscopy and scanning tunneling microscopy. The conclusion is that the polymeric film consists of crystalline and amorphous phases. Spherul...
12242332
Insig-2, a second endoplasmic reticulum protein that binds SCAP and blocks export of sterol regulatory element-binding proteins.
This paper describes insig-2, a second protein of the endoplasmic reticulum that blocks the processing of sterol regulatory element-binding proteins (SREBPs) by binding to SCAP (SREBP cleavage-activating protein) in a sterol-regulated fashion, thus preventing it from escorting SREBPs to the Golgi. By blocking this move...
12239343
A method for the generation of combinatorial antibody libraries using pIX phage display.
For more than a decade, phage displayed combinatorial antibody libraries have been used to generate and select a wide variety of antibodies. We previously reported that the phage coat proteins pVII and pIX could be used to display the heterodimeric structure of the antibody Fv region. Herein, aspects of this technology...
12388423
Endothelin-1 activates mesangial cell ERK1/2 via EGF-receptor transactivation and caveolin-1 interaction.
Endothelin-1 (ET-1) stimulates glomerular mesangial cell proliferation and extracellular matrix protein transcription through an ERK1/2-dependent pathway. In this study, we determined whether ET-1 activation of glomerular mesangial cell ERK1/2 is mediated through EGF receptor (EGF-R) transactivation and whether intact ...
12237412
Molecular basis for the explanation of the exponential growth of polyelectrolyte multilayers.
The structure of poly(l-lysine) (PLL)/hyaluronan (HA) polyelectrolyte multilayers formed by electrostatic self-assembly is studied by using confocal laser scanning microscopy, quartz crystal microbalance, and optical waveguide lightmode spectroscopy. These films exhibit an exponential growth regime where the thickness ...
12374572
Modeling molecular networks: a systems biology approach to gene function.
A report on the European Science Foundation Workshop on Modeling of Molecular Networks, Granada, Spain, 11-14 June 2002.
12235356
Nanocrystal targeting in vivo.
Inorganic nanostructures that interface with biological systems have recently attracted widespread interest in biology and medicine. Nanoparticles are thought to have potential as novel intravascular probes for both diagnostic (e.g., imaging) and therapeutic purposes (e.g., drug delivery). Critical issues for successfu...
12235142
Interactions of STAT3 with caveolin-1 and heat shock protein 90 in plasma membrane raft and cytosolic complexes. Preservation of cytokine signaling during fever.
Interleukin-6 (IL-6) initiates STAT3 signaling in plasma membrane rafts with the subsequent transit of Tyr-phosphorylated STAT3 (PY-STAT3) through the cytoplasmic compartment to the nucleus in association with accessory proteins. We initially identified caveolin-1 (cav-1) as a candidate STAT3-associated accessory prote...
12231507
Coordinated methyl and RNA binding is required for heterochromatin localization of mammalian HP1alpha.
In mammalian cells, as in Schizosaccharomyces pombe and Drosophila, HP1 proteins bind histone H3 tails methylated on lysine 9 (K9). However, whereas K9-methylated H3 histones are distributed throughout the nucleus, HP1 proteins are enriched in pericentromeric heterochromatin. This observation suggests that the methyl-b...
12232051
Circuits and programmable self-assembling DNA structures.
Self-assembly is beginning to be seen as a practical vehicle for computation. We investigate how basic ideas on tiling can be applied to the assembly and evaluation of circuits. We suggest that these procedures can be realized on the molecular scale through the medium of self-assembled DNA tiles. One layer of self-asse...
12392599
Optimisation of batch culture conditions for cyclodextrin glucanotransferase production from Bacillus circulans DF 9R.
BACKGROUND: The extracellular enzyme cyclodextrin glucanotransferase (CGTase) synthesizes cyclic malto-oligosaccharides called cyclodextrins (CDs) from starch and related alpha-1,4-glucans. CGTases are produced by a variety of bacteria, mainly Bacillus species, by submerged culture in complex medium. CGTases differ in ...
12373393
Porphyrin binding to DNA investigated by cyclodextrin supramolecular system.
The interactive mode of meso-tetrakis- (4- N-trimethylaminobenzyl) porphyrin (TAPP) with DNA has been investigated by the cyclodextrin (CD)-porphyrin supramolecular system. The binding of TAPP with DNA is inhibited by the anion CD derivative, sulfurbutyl-beta-cyclodextrin (SB-beta-CD); however, the neutral CD cannot in...
12373394
First- and second-order multivariate calibration applied to biological samples: determination of anti-inflammatories in serum and urine.
First- and second-order multivariate calibration of fluorescence data have been compared as regards the determination of anti-inflammatories and metabolites in the biological fluids serum and urine. The simultaneous resolution of naproxen-salicylic acid mixtures in serum and naproxen-salicylic acid-salicyluric acid mix...
12226795
Gene expression phenotype in heterozygous carriers of ataxia telangiectasia.
The defining characteristic of recessive diseases is the absence of a phenotype in the heterozygous carriers. Nonetheless, subtle manifestations may be detectable by new methods, such as expression profiling. Ataxia telangiectasia (AT) is a typical recessive disease, and individual carriers cannot be reliably identifie...
12221072
The role of the Tim8p-Tim13p complex in a conserved import pathway for mitochondrial polytopic inner membrane proteins.
Tim23p is imported via the TIM (translocase of inner membrane)22 pathway for mitochondrial inner membrane proteins. In contrast to precursors with an NH2-terminal targeting presequence that are imported in a linear NH2-terminal manner, we show that Tim23p crosses the outer membrane as a loop before inserting into the i...
12218175
Crystal structure of calcineurin-cyclophilin-cyclosporin shows common but distinct recognition of immunophilin-drug complexes.
Calcineurin, a Ca2+/calmodulin-dependent protein phosphatase, is the common target for two immunophilin-immunosuppressant complexes, cyclophilin A-cyclosporin A (CyPA-CsA) and FKBP-FK506. How the two structurally distinct immunophilin-drug complexes bind the same target has remained unknown. We report the crystal struc...
12213186
Growth of Helicobacter pylori in a long spiral form does not alter expression of immunodominant proteins.
<h4>Background</h4>We have previously reported that altered culture conditions (a broth media with shaking) could induce a strain of Helicobacter pylori to assume a long spiral morphology resembling that described for Helicobacter heilmannii. The present study was initiated to determine if other strains of H. pylori co...
12244310
Staging and resetting T cell activation in SMACs.
During the productive interaction of T cells with antigen-presenting cells (APCs), engaged receptors, including the T cell antigen receptors and their associated tyrosine kinases, assemble into spatially segregated supramolecular activation clusters (SMACs) at the area of cell contact. Here, we studied intracellular si...
12209019
Comparison of different labeling methods for two-channel high-density microarray experiments.
In this report we evaluate three methods for labeling nucleic acids to be hybridized to a cDNA microarray: direct labeling, indirect amino-allyl labeling, and the dendrimer labeling method (Genisphere). The dendrimer method requires the smallest quantity of sample, 2.5 microg of total RNA compared with 20 microg with t...
23345790
Molecular evolution in static and dynamical landscapes.
In an attempt to understand protein evolution, we address the issues ofhow much variety in the sequences is needed to prompt the evolution ofan enzyme from random polypeptides and how does cellular interactionaffect the dynamics of molecular evolution to allow genetic diversity inpopulation. The experimental evolution ...
18968770
Cesium ion selective electrode based on calix[4]crown ether-ester.
The potentiometric response characteristics of cesium ion selective PVC membrane electrode employing calix[4]crown ether-ester as an ionophore were investigated. The electrode exhibit a good response for cesium ion over wide concentration range of 5.0x10(-6)-1.0x10(-1) M with a Nernstian slope of 59 mV per decade. The ...
16358689
[Capillary electrophoretic enantioseparation of arylglycine amides with highly sulfated beta-cyclodextrin as chiral selector].
Enantiomers of nine arylglycine amides synthesized were successfully separated by capillary electrophoresis (CE) using highly sulfated beta-cyclodextrin (HS-beta-CD) as a chiral selector. Baseline enantioseparation of the analytes was obtained within 6 min at neutral pH but not the commonly used acidic condition. HS-be...
15803645
Perspectives on biotechnological applications of archaea.
Many archaea colonize extreme environments. They include hyperthermophiles, sulfur-metabolizing thermophiles, extreme halophiles and methanogens. Because extremophilic microorganisms have unusual properties, they are a potentially valuable resource in the development of novel biotechnological processes. Despite extensi...
12553899
Hydroxypropyl-beta-cyclodextrin-flutamide inclusion complex. II. Oral and intravenous pharmacokinetics of flutamide in the rat.
<h4>Purpose</h4>The objective of this work was to determine the pharmacokinetics of flutamide (FLT) and its active metabolite, 2-hydroxy-flutamide (FLT-2-OH) in rats, following formulation in hydroxypropyl-Beta-cyclodextrin (FLT-HPBetaCyD).<h4>Methods</h4>The pharmacokinetics of FLT-HPBetaCyD, FLT-suspension (FLT-SUSP)...
12470279
High throughput synthesis of ester library utilizing selective molecular reactivity and recognition technology.
This paper reports a new solid support reagent that showed high degrees of selective molecular reactivity and molecular recognition in homo-functional reactions (reactions having similar reactive functionality in reactants and products).
12470273
High-density synthetic peptide microarrays: emerging tools for functional genomics and proteomics.
New approaches for manufacturing and application of peptide arrays on planar surfaces are emerging, thereby opening advanced opportunities to probe the expression and function of the proteome. In complementing DNA and protein array analyses, peptide fragment screening directly addresses functional protein interaction s...
12470272
High molecular recognition: design of "Keys".
Molecular recognition between molecules is one of the most fundamental processes in biology and chemistry. The recognition process is largely driven by non-covalent forces such as hydrogen bonding, electrostatics, van der Waals forces, pi-pi interactions, and conformational energy. The complementarity between the recep...
12469808
A study of a moleculartweezer host-guest system by a combination of quantum-chemical calculations and solid-state NMR experiments.
A study of a host-guest system consisting of a naphthalene-spaced tweezer with a 1,4 dicyanobenzene guest molecule is presented. The complex is investigated using a combination of quantum-chemical calculations and solid-state NMR experiments. The advantages of such an approach are illustrated. The focus is on the calcu...
12447912
Dealing with intractable protein cores: protein sequencing of the Mcg IgG and the Yvo IgM heavy chain variable domains.
The VH domains of two human monoclonal antibodies, designated Mcg IgG1(lambda) and Yvo IgM(kappa), were particularly intractable to standard protein sequencing protocols. Peptides liberated from the VH domains of these proteins, using standard enzymatic or chemical cleavages, invariably precipitated during the procedur...
12447911
Mcg light chain dimer as a model system for ligand design: a docking study.
Mcg light chain dimer has been extensively studied by crystallography and peptide binding studies to investigate its peptide cross-reactivity as well as to use it as a model system for designing space filling peptide ligands. Here we extend these investigations by utilizing automated docking. Mcg light chain dimer is a...
12447910
Expression and functional analysis of recombinant scFv and diabody fragments with specificity for human RhD.
In an attempt to generate recombinant anti-D reagents for possible diagnostic and therapeutic use we cloned the genes encoding the variable (V) domains of a human anti-D antibody secreted by the lymphoblastoid cell line BTSN4. A single-chain Fv (scFv) fragment was constructed using a 21 amino acid linker to join the ge...
12447909
Bifluorophoric molecules as fluorescent beacons for antibody-antigen binding.
The quenching of fluorescence (up to 98%) by anti-fluorescein antibodies is well documented in the literature. Here we report a system where, instead of quenching, bifluorophoric molecules are designed to increase in fluorescence upon binding by an anti-fluorescein antibody. Bifluorophoric molecules are made of fluores...
12447908
Combinatorial methods for discovery of peptide ligands which bind to antibody-like molecules.
In the 1980s, new methods of parallel peptide synthesis were used to make large libraries of peptides, which were then screened for binding to Bence-Jones dimers. Subsequent X-ray crystallography of the Bence-Jones proteins, which had been infiltrated with peptide ligand, was used to determine the structural correlate ...
12447907
Mcg in 2030: new techniques for atomic position determination of immune complexes.
The lambda-type light chain dimer from a patient (Mcg) with multiple myeloma and amyloidosis was a pioneer protein for determining the three-dimensional structures of immunoglobulins, understanding the effects of ligand binding, and exploring the use of combinatorial methods to identify novel peptides complementary to ...
12447906
Structural and functional comparisons between vanadium haloperoxidase and acid phosphatase enzymes.
The crystallographic structures of both the vanadium chloroperoxidase and bromoperoxidase enzymes have been determined with either vanadium or phosphate bound at their active site. The amino acids that are involved in phosphate binding in the acid phosphatase enzymes and those that are coordinated to vanadium in the ha...
12447905
Structurally adaptive hot spots at a protein interaction interface on TRAF3.
Tumor necrosis factor (TNF) signaling is controlled by receptors and intracellular signaling pathways that activate the NF-kappaB transcription factor. The resulting signals elicit immune responses and have important implications for disorders such as autoimmunity or allergic reactions. TNF-receptor-associated factors ...
12447904
Cyclosporin A as a model antigen: immunochemical and structural studies.
The immunosuppressant drug cyclosporin (Cs) A is a cyclic undecapeptide which has been used as a model antigen because structural information and a large number of analogs, modified at each of its 11 positions, were available. This review summarizes immunochemical and crystallographic studies of the interaction between...
12447903
Inhibition of HIV protease by monoclonal antibodies.
The protease of HIV plays a critical role in the maturation of the infectious particles of the virus. The enzyme has therefore been extensively studied with the objective of developing therapeutics that inhibit viral proliferation. We have produced monoclonal antibodies specific for the HIV-1 protease, and selected tho...
12447902
Structural, antigenic and evolutionary analyses of immunoglobulins and T cell receptors.
We have had the pleasure of collaborating with Allen Edmundson for the past 15 years on the structure, binding properties and evolution of immunoglobulins and T cell receptors. Among the most significant contributions of our joint efforts were: (1) the predictive use of structural features of immunoglobulin domains to ...
12447901
Crystal structures of human antibodies: a detailed and unfinished tapestry of immunoglobulin gene products.
Sequencing of all human immunoglobulin (Ig) germline gene segments has recently been completed. However, our first glimpses of the recombined products of this combinatorial gene system were in the 1970s, in landmark publications, reporting the crystal structures of two human myeloma proteins, the Mcg lambda light chain...
12447900
Reductionism and the search for structure-function relationships in antibody molecules.
One of the claims of reductionism is that it can explain all the features of living systems by an analysis of their physico-chemical constituents. Such a claim disregards the existence in biological systems of emergent properties that do not exist in their isolated components but which allow autonomous organisms to be ...
12440774
The functional role of poly(ADP-ribose)polymerase 1 as novel coactivator of NF-kappaB in inflammatory disorders.
Mammalian poly(ADP-ribose)polymerase 1 (PARP-1) is an abundant nuclear chromatin-associated protein and belongs to a large family of enzymes that catalyzes the transfer of ADP-ribose units from its substrate beta-nicotinamide adenine dinucleotide (NAD+) covalently to itself and other nuclear chromatin-associated protei...
12408677
Cholesterol attenuates the membrane perturbing properties of beta-amyloid peptides.
Growing evidence indicates a significant linkage between Abeta and cholesterol metabolism, although the exact role of cholesterol in brain aging and in the pathogenesis of AD is still unknown. Recently, in vitro and in vivo modification of cell cholesterol and its effect on Abeta-generation became a straight focus in t...
12403067
Design and function of a dendrimer-based therapeutic nanodevice targeted to tumor cells through the folate receptor.
<h4>Purpose</h4>We sought to develop nanoscale drug delivery material that would allow targeted intracellular delivery while having an imaging capability for tracking uptake of the material. A complex nanodevice was designed and synthesized that targets tumor cell through the folate receptor.<h4>Methods</h4>The device ...
12403066
Evaluation of strategies for the intracellular delivery of proteins.
<h4>Purpose</h4>The intracellular delivery of functionally active protein represents an important emerging strategy for laboratory investigation and therapeutic applications. Although a number of promising approaches for protein delivery have been developed, thus far there has been no attempt to compare the merits of t...
12396628
A nonionic amphiphile agent promotes gene delivery in vivo to skeletal and cardiac muscles.
Direct injection of naked DNA into skeletal or cardiac muscle induces detectable gene expression. Although this provides a practical system for transgene expression, the reported efficacy is too low to confer a therapeutic benefit. By following a rational strategy based on the supramolecular structures adopted by activ...
12378956
Cyclodextrin complex osmotic tablet for glipizide delivery.
Poorly soluble glipizide was selected as the model drug to prepare osmotic pump tablets (OPT) with proper accessorial material after it was made an inclusion complex by kneading method in order to increase solubility. Polyethylene glycol 4000 (PEG4000) and cellulose acetate (CA) were selected as the coating materials, ...
12373770
Simultaneous determination of dopa and carbidopa enantiomers by capillary zone electrophoresis.
Dopa and carbidopa, components of the dual therapy for Parkinson's disease treatment, are both provided as single enantiomers, since their D-forms are inactive. To ensure the efficiency and safety of the therapy, these D-enantiomers, therefore, should be considered as impurities. In this paper, the enantioseparation po...
12369452
Effect of pH and complexation on transdermal permeation of gliquidone.
Gliquidone, a second generation sulfonylurea has been investigated for transdermal delivery. The poor aqueous solubility of the drug prompted the use of hydroxypropyl-beta-cyclodextrin (HP-beta-CD), a cyclic oligosaccharide, which is known to facilitate transdermal permeation of many drugs by enhancing the solubility a...
12374091
Syntheses, electronic absorption, emission, and ion-binding studies of platinum(III) C empty set N empty set C and terpyridyl complexes containing crown ether pendants.
A series of platinum (II) C empty set N empty set C complexes, [Pt(C empty set N empty set C) (L)] (HC empty set N empty set CH=2,6-diphenylpyridine (dppy); L=Ph(2)PB15C5 (1, B15C5=benzo[15]crown-5), Ph(2)PDMP (2, DMP=3,4-dimethoxyphenyl), pyCOA15C5 (3, A15C5=aza[15]crown-5), pyCON(CH(2)CH(2)OCH(3))(2) (4), pyC[triple ...
12360944
Metal-induced supramolecualr chirality in an optically active polythiophene aggregate.
Chiral polythiophenes (PTs), in sharp contrast to other optically active polymers, exhibit optical activity in the pi-pi* transition region which is derived from the chirality of the main chain when they self-assemble to form a supramolecular pi-stacked aggregate with intermolecular interactions in a poor solvent or in...
12360934
Probing the limit of weak host-guest interactions: insertion compounds of mercury(II) halides with microporous SiO(2) hosts.
Mercury(II) halides HgX(2) (X=Cl, Br, I) were inserted into the voids of the crystalline microporous SiO(2) modifications deca-dodecasil 3R (short term: DDR), silica-theta-1 (TON), silica-ferrierite (FER) and silicalite-1 (MFI) by vapour phase loading. The properties of the occluded guest species were studied by X-ray ...
12360933
Heterodinuclear Ln[bond]Na complexes with an asymmetrical macrocyclic compartmental Schiff base.
Heterodinuclear lanthanide(III)-sodium(I) complexes [LnNa(L)(Cl)(2)(CH(3)OH)] (Ln=La[bond]Nd, Sm[bond]Lu), where H(2)L is a [1+1] asymmetric compartmental macrocyclic ligand containing a N(3)O(2) Schiff base and a O(3)O(2) crown-ether-like coordination site, have been prepared and characterized by IR, (1)H, (13)C, and ...
12357819
A twenty-four membered mixed-metal macrocycle; synthesis and structure of cyclo-[(3-Me-1,2-C6H3O2)2SbNa(THF)2]6.
The first example of a twenty-four membered mixed p-/s-block macrocycle, cyclo-[(3-Me-1,2-C6H3O2)2SbNa(THF)2]6 1 has been synthesised and structurally characterised from the reaction between 3-Me-1,2-C6H3(OH)(ONa) and (Me2N)2Sb(CH2)3Sb(NMe2)2.
12357818
Fullerene sensors based on calix[5]arene.
A new class of fullerene sensors based on calix[5]arenes has produced the highly sensitive detection of C60 and C70.
12357805
Dynamic dendrimer at electrified interface: potential dependent adsorption-desorption and reorientation of a 4-pyridyl-modified PAMAM dendrimer.
Potential-dependent dynamic adsorption-desorption and reorientation of a 4-pyridyl modified PAMAM G2 dendrimer at a Au(111) electrode has been demonstrated.
12357783
Replication of dendrimer monolayer as nanopores in titania ultrathin film.
An ultrathin titania film with molecular-sized cavities was synthesized by treating a ca. 8 nm thick (TiO2)3(dendrimer)(TiO2)2 sandwich film with activated oxygen gas.
12362906
Monocarbaborane anion chemistry. An interesting encapsulation of the Pd2I2(P(C6H(4)-4-Me)3)4]2+ cation by a pair of [PhCB9H4I(C6H4Me)4]- anions.
Reaction of the [1-Ph-closo-1-CB9H(4)-6,7,8,9,10-I5]- anion with 4-MeC6H4MgBr in the presence of [PdCl2(PPh3)2] gives the [Pd2I2(P(C6H(4)-4-Me)3)4]2+ salt of the [1-Ph-closo-1-CB9H(4)-10-I-6,7,8,9-(C6H(4)-4-Me)4]- anion, which exhibits an unusual neutral supramolecular assembly in the solid state, in which the dipallad...
12357768
Dynamic aspects in host-guest complexation by coordination nanotubes.
Rod-like guests accommodated in self-assemble coordination nanotubes are shown to stay in the tubes without flipping along its length at room temperature, but rapidly exchange intermolecularly at high temperature.
12357766
Luminescent terbium(III) complexes with pendant crown ethers responding to alkali metal ions and aromatic antennae in aqueous solution.
The luminescence lifetime of TbL2 with a pendant 15-crown-5 increased by 65% to 2.95 ms with an [Na+] concentration of 0.13 M in aqueous solution; the maximum amplification of the luminescence intensity of TbL1 containing aza-15-crown-5 reached a factor of 47 upon addition of the aromatic antenna p-chlorobenzoate 1.