Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.2.1.1 (ACS)
 78,556 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The microcystin family of toxins is the most common cause of hepatotoxicity associated with water blooms of cyanobacterial genera. The biosynthetic assembly line producing the toxic cyclic peptide, microcystin, contains an adenylation-peptidyl carrier protein didomain (A-PCP) at the N-terminus of the initiator module McyG (295 kDa) that has been postulated to activate and load the starter unit phenylacetate for formation of the unusual aromatic beta-amino acid residue, Adda, before subsequent extension. Characterization of the McyG A-PCP didomain (78 kDa) using ATP-PP i exchange assays and mass spectrometry revealed that assorted phenylpropanoids are preferentially activated and loaded onto the PCP carrier domain rather than phenylacetate itself. For the first time, thioesters formed in vivo were detected directly using large molecule mass spectrometry. Additionally substrates were cleaved using a type II thioesterase for structural elucidation by small molecule mass spectrometry. Unprecedented features of the McyG A-PCP didomain include the in vivo acylation of the holo PCP with exogenous and endogenous substrates, along with the ability of the apo protein to retain the acyl-AMP intermediate during affinity purification. These results imply that phenylpropanoids are preferentially loaded onto the McyG PCP; however one carbon must be excised following extension of the starter unit with malonyl-CoA in order to generate the expected polyketide chain which leads us to ponder the novel biochemistry by which this occurs.
ACS Chem Biol 2006 Mar 17
PMID:Structural characterization of in vitro and in vivo intermediates on the loading module of microcystin synthetase. 1716 49

Recently, chemically synthesized short interfering RNA (siRNA) duplexes have been used with success for gene silencing. Chemical modification is desired for therapeutic applications to improve biostability and pharmacokinetic properties; chemical modification may also provide insight into the mechanism of silencing. siRNA duplexes containing the 2,4-difluorotoluyl ribonucleoside (rF) were synthesized to evaluate the effect of noncanonical nucleoside mimetics on RNA interference. 5'-Modification of the guide strand with rF did not alter silencing relative to unmodified control. Internal uridine to rF substitutions were well-tolerated. Thermal melting analysis showed that the base pair between rF and adenosine (A) was destabilizing relative to a uridine-adenosine pair, although it was slightly less destabilizing than other mismatches. The crystal structure of a duplex containing rFoA pairs showed local structural variations relative to a canonical RNA helix. As the fluorine atoms cannot act as hydrogen bond acceptors and are more hydrophobic than uridine, there was an absence of a well-ordered water structure around the rF residues in both grooves. siRNAs with the rF modification effectively silenced gene expression and offered improved nuclease resistance in serum; therefore, evaluation of this modification in therapeutic siRNAs is warranted.
ACS Chem Biol 2006 Apr 25
PMID:Gene silencing activity of siRNAs with a ribo-difluorotoluyl nucleotide. 1716 65

The remarkable progress of cryo-electron microscopy and crystallography in elucidating ribosomal structure and function continues. Most recently, two papers about complete 70S ribosomes from Thermus thermophilus at 2.8- and 3.7-A resolution give us more details about the conformations of bound transfer RNA (tRNA) molecules; the bridges between subunits; the locations and roles of proteins, magnesium ions, and water molecules; and the dynamics of ribosomes. Very significant new insights have been gained, particularly for the tRNAs, which can only be studied in their entirety in full ribosomes.
ACS Chem Biol 2006 Oct 24
PMID:Deepening ribosomal insights. 1716 51

The ion exchange membrane bioreactor (IEMB) proved to be an effective technology for the removal of nitrate and perchlorate from polluted drinking water when using a mono-anion permselective membrane such as Neosepta ACS. Aiming at reducing the cost of the system, this study evaluates the use of a lower-cost anion exchange membrane, which exhibits no preferential mono-anion permselective properties. With this purpose an Excellion I-200 membrane was tested, for the removal of anionic micropollutants, such as nitrate and perchlorate from drinking water supplies. The impact of the lower anion permselectivity of this membrane on the quality of the treated water was determined. It was demonstrated that differences between the membrane properties are responsible for the different permselectivities observed towards multi-valent and mono-valent anions. The use of Excellion I-200 resulted in a less selective removal of perchlorate and nitrate, allowing anions such as sulphate and phosphate species to be transported. When treating 3.1l/m(2)h of water contaminated with 100microg/l of perchlorate and 60mg/l of nitrate, lower removal degrees were obtained (85% of perchlorate and 88% of nitrate), compared with 96% of perchlorate and 99% of nitrate achieved with the Neosepta ACS membrane, operating under the same conditions. However, the Excellion I-200 membrane shows no target anion flux decline during a relatively long period of operation (1 month) and no secondary contamination of the treated water by the carbon source used. These characteristics are essential for a membrane to be successfully used in the IEMB system. Additionally, the selection of the membrane depends on the latter characteristics and on the water quality requirements.
Water Res 2008 Mar
PMID:Removal of mono-valent oxyanions from water in an ion exchange membrane bioreactor: influence of membrane permselectivity. 1805 85

Suspensions (20%) of microfine and ACS grade zinc oxide, or 20% titanium oxide in water, castor oil or polyethylene glycol were applied topically to rabbit skin over 4 h (1 day) or 2 h daily (3 days). Skin sites were analysed for metal uptake. Percutaneous absorption of the oxides was probably low, most remaining on the skin surface. Uptake patterns were influenced by the vehicles used. Appreciably more microfine zinc oxide was taken up by the skin in subacute studies. Local changes in trace metal concentration were construed as evidence of percutaneous absorption of zinc and titanium oxides. Further studies are indicated to validate the significance of these preliminary observations.
 ...
PMID:Zinc and titanium oxides: promising UV-absorbers but what influence do they have on the intact skin? 1850 34

Real-time study of the transport and biocompatibility of nanomaterials in early embryonic development at single-nanoparticle resolution can offer new knowledge about the delivery and effects of nanomaterials in vivo and provide new insights into molecular transport mechanisms in developing embryos. In this study, we directly characterized the transport of single silver nanoparticles into an in vivo model system (zebrafish embryos) and investigated their effects on early embryonic development at single-nanoparticle resolution in real time. We designed highly purified and stable (not aggregated and no photodecomposition) nanoparticles and developed single-nanoparticle optics and in vivo assays to enable the study. We found that single Ag nanoparticles (5-46 nm) are transported into and out of embryos through chorion pore canals (CPCs) and exhibit Brownian diffusion (not active transport), with the diffusion coefficient inside the chorionic space (3 x 10(-9) cm(2)/s) approximately 26 times lower than that in egg water (7.7 x 10(-8) cm(2)/s). In contrast, nanoparticles were trapped inside CPCs and the inner mass of the embryos, showing restricted diffusion. Individual Ag nanoparticles were observed inside embryos at each developmental stage and in normally developed, deformed, and dead zebrafish, showing that the biocompatibility and toxicity of Ag nanoparticles and types of abnormalities observed in zebrafish are highly dependent on the dose of Ag nanoparticles, with a critical concentration of 0.19 nM. Rates of passive diffusion and accumulation of nanoparticles in embryos are likely responsible for the dose-dependent abnormalities. Unlike other chemicals, single nanoparticles can be directly imaged inside developing embryos at nanometer spatial resolution, offering new opportunities to unravel the related pathways that lead to the abnormalities.
ACS Nano 2007 Sep
PMID:In vivo imaging of transport and biocompatibility of single silver nanoparticles in early development of zebrafish embryos. 1912 72

A marine natural product extract library has been screened with a functional cell-based G-protein coupled receptor assay to find compounds capable of binding the human cannabinoid receptors CB1 and CB2. The methanol extract of the marine sponge Dasychalina fragilis collected in Papua New Guinea was active in the assay. Bioassay-guided fractionation of the extract identified the phosphorylated sterol sulfate haplosamate A (1) as a cannabinoid receptor agonist. The high water solubility of haplosamate A (1) allowed exploration of its binding interactions with the human cannabinoid receptors in whole insect cells by means of saturation transfer double-difference NMR spectroscopy. This technique confirmed that haplosamate A (1) binds selectively to these receptors.
ACS Chem Biol 2009 Feb 20
PMID:Functional cell-based screening and saturation transfer double-difference NMR have identified haplosamate A as a cannabinoid receptor agonist. 1917 6

We show that large surface areas exist for supramolecular chemistry on single-walled carbon nanotubes (SWNTs) prefunctionalized noncovalently or covalently by common surfactant or acid-oxidation routes. Water-soluble SWNTs with poly(ethylene glycol) (PEG) functionalization via these routes allow for surprisingly high degrees of pi-stacking of aromatic molecules, including a cancer drug (doxorubicin) with ultrahigh loading capacity, a widely used fluorescence molecule (fluorescein), and combinations of molecules. Binding of molecules to nanotubes and their release can be controlled by varying the pH. The strength of pi-stacking of aromatic molecules is dependent on nanotube diameter, leading to a method for controlling the release rate of molecules from SWNTs by using nanotube materials with suitable diameter. This work introduces the concept of "functionalization partitioning" of SWNTs, i.e., imparting multiple chemical species, such as PEG, drugs, and fluorescent tags, with different functionalities onto the surface of the same nanotube. Such chemical partitioning should open up new opportunities in chemical, biological, and medical applications of novel nanomaterials.
ACS Nano 2007 Aug
PMID:Supramolecular chemistry on water-soluble carbon nanotubes for drug loading and delivery. 1920 29

We explored advantages of diverse carbon nanotube forests with tailored structures synthesized by water-assisted chemical vapor deposition (CVD) growth (supergrowth) from engineered catalysts. By controlling the catalyst film thickness, we synthesized carbon nanotube (CNT) forests composed from nanotubes with different size and wall number. With extensive characterizations, many interesting dependencies among CNT forest structures and their properties, which were unknown previously, were found. For example, multiwalled carbon nanotubes (MWNTs) showed superior electronic conductivity while single-walled carbon nanotubes (SWNTs) showed superior thermal diffusivity, and sparse MWNTs achieved lower threshold voltage for field emission than dense SWNTs. These interesting trends highlight the complexity in designing and choosing the optimum CNT forest for use in applications.
ACS Nano 2009 Jan 27
PMID:Exploring advantages of diverse carbon nanotube forests with tailored structures synthesized by supergrowth from engineered catalysts. 1920 56

Compared with noble metals and quantum dots, dielectric complex oxide nanoparticles are significantly less popular due to their high crystallization temperature, making difficult their synthesis in the 10-100 nm range for which surface effects are reduced. We report here an original process permitting thermal annealing of complex oxide nanoparticles at high temperature without aggregation and growth. Thus, after thermal treatment, these annealed particles can be dispersed in water, leading to concentrated aqueous colloidal dispersions containing isolated highly crystalline particles. This contrasts with usual colloidal techniques for which the production of particles in the 10-100 nm range generally leads to poorly crystallized particles, especially for multicomponent oxides. From two examples, we show some possibilities offered by this type of process. This concerns the synthesis of lanthanide-doped oxide nanoparticles exhibiting a bulk behavior for their luminescence properties and the control of the composition in nitrogen-doped titanium oxide particles without sintering and size change.
ACS Nano 2008 Dec 23
PMID:High temperature strategy for oxide nanoparticle synthesis. 1920 85


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>