BI-32169, a bicyclic 19-peptide with strong glucagon receptor antagonist activity from Streptomyces sp.

A new bicyclic 19-peptide, BI-32169, has been isolated from the culture broth of Streptomyces sp. (DSM 14996). Its structure has been established by amino acid analysis, mass spectrometry, and 2D NMR analysis.

NMR-driven discovery of benzoylanthranilic acid inhibitors of far upstream element binding protein binding to the human oncogene c-myc promoter.

Reversal of aberrant gene expression that is induced by the proto-oncogene c-myc is likely to be effective for treating a variety of tumors that rely on this pathway for growth. One strategy to down-regulate the c-myc pathway is to target transcription factors that regulate its own expression. A host of proteins act in coordination to regulate c-myc expression and any one of them are theoretical targets for small-molecule therapy.

In vivo heme scavenging by Staphylococcus aureus IsdC and IsdE proteins.

We report the first characterization of the in vivo porphyrin scavenging abilities of two components of a newly discovered heme scavenging system involving iron-regulated surface determinant (Isd) proteins. These proteins are present within the cell envelope of the Gram-positive human pathogen Staphylococcus aureus. IsdC and IsdE, when expressed heterologously in Escherichia coli, efficiently scavenged intracellular heme and resulted in de novo heme synthesis in excess of 100-fold above background.

Structure of the N-terminal RNA-binding domain of the SARS CoV nucleocapsid protein.

The severe acute respiratory syndrome (SARS) virus belongs to the Coronaviridea family of viruses. Its virion encodes several proteins including a replicase and four structural proteins. Here we describe the three-dimensional structure of the N-terminal domain of the SARS coronavirus (CoV) nucleocapsid protein.

Molecular satellite dishes: attaching parabolic and planar arenes to heterofullerenes.

The electrophilic attack of C(59)N(+) on arenes such as pyrene, coronene and corannulene leads to the regioselective formation of fullerene conjugates, in which polycyclic aromatics are connected to the spherical heterofullerene by a single sigma-bond.

SOS-NMR: a saturation transfer NMR-based method for determining the structures of protein-ligand complexes.

An NMR-based alternative to traditional X-ray crystallography and NMR methods for structure-based drug design is described that enables the structure determination of ligands complexed to virtually any biomolecular target regardless of size, composition, or oligomeric state. The method utilizes saturation transfer difference (STD) NMR spectroscopy performed on a ligand complexed to a series of target samples that have been deuterated everywhere except for specific amino acid types. In this way, the amino acid composition of the ligand-binding site can be defined, and, given the three-dimensional structure of the protein target, the three-dimensional structure of the protein-ligand complex can be determined.

A strategy for high-throughput assay development using leads derived from nuclear magnetic resonance-based screening.

A strategy is described for the development of high-throughput screening assays against targets of unknown function that involves the use of nuclear magnetic resonance (NMR) spectroscopy. Using this approach, molecules that bind to the protein target are identified from an NMR-based screen of a library of substrates, cofactors, and other compounds that are known to bind to many proteins and enzymes. Once a ligand has been discovered, a fluorescent or radiolabeled analog of the ligand is synthesized that can be used in a high-throughput screen.

Solution structure and function of an essential CMP kinase of Streptococcus pneumoniae.

Streptococcus pneumoniae is a major human pathogen that causes high mortality and morbidity and has developed resistance to many antibiotics. We show that the gene product from SP1603, identified from S. pneumoniae TIGR4, is a CMP kinase that is essential for bacterial growth.

Fullerene-acene chemistry: single-crystal X-ray structures for a [60]fullerene-pentacene monoadduct and a cis-bis[60]fullerene adduct of 6,13-diphenylpentacene.

[structure: see text]. Crystal structures of the cis-bis[60]fullerene adduct of 6,13-diphenylpentacene (with the closest carbon atoms on adjacent fullerenes only 3.065(8) angstroms apart) and the [60]fullerene-pentacene monoadduct are in remarkably close agreement with the MM2 calculated structures.

Spectroscopy and electronic structure of electron deficient zinc phthalocyanines.

The effect of introduction of perfluoro alkyl groups into phthalocyanines, as evidenced by the spectroscopic properties of 1,4,8,11,15,18,22,25-octa-fluoro-2,3,9,10,16,17,23,24-octa-perfluoro isopropyl zinc phthalocyanine, ZnF(64)Pc(-2) and its ring-reduced radical anion species, [ZnF(64)Pc(-3)](-), are reported. A combination of UV-visible absorption and magnetic circular dichroism (MCD) spectroscopy, ESI and MALDI-TOF mass spectrometry, cyclic and differential pulse voltammetry, and complete theoretical calculations using INDO/S and DFT techniques reveals that the substitution of all sixteen hydrogen atoms in protio ZnPc(-2) by eight F and eight i-C(3)F(7) groups red shifts the Q and pi --> pi transitions and narrows the HOMO-LUMO gap while simultaneously preventing ring photooxidation and stabilizing the radical anion. The [ZnF(64)Pc(-3)](-) species, which is in equilibrium in solution with the neutral complex when a reducing agent is present, is unusually stable.

Altered serotonin immunoreactivities in the left colon of patients with colonic inertia.

BACKGROUND: Serotonin is an important positive regulator of colonic motility and transit. Its quantity and distribution in the left colon could be abnormal in patients with colonic inertia (CI) and contribute to the disease. AIM: To evaluate serotonin positive cells and immuno-reactivities in the mucosa, submucosa and muscularis propria of the left colon from patients with CI was compared to a control group.

Hoxb13 knockout adult skin exhibits high levels of hyaluronan and enhanced wound healing.

In contrast to adult cutaneous wound repair, early gestational fetal cutaneous wounds heal by a process of regeneration, resulting in little or no scarring. Previous studies indicate that down-regulation of HoxB13, a member of the highly conserved family of Hox transcription factors, occurs during fetal scarless wound healing. No down-regulation was noted in adult wounds.

Iatrogenic pleuropulmonary charcoal instillation in a teenager.

Activated charcoal given through a nasogastric tube is a standard intervention for many types of toxic ingestions in the emergency department. This case study describes a teenage girl whose multidrug overdose was complicated by accidental charcoal instillation into her left lung and pleural space through a misplaced nasogastric tube. The ensuing empyema did not respond to antibiotic therapy alone, probably due to the inherent properties of charcoal, and required a chest tube placement with continuous irrigation.

Shock-like sensations during venlafaxine withdrawal.

Electric shock-like sensations may occur after cessation of treatment with serotonin selective reuptake inhibitors but are reported in the literature only rarely with discontinuation of venlafaxine. Two patients experienced severe shock-like sensations during venlafaxine withdrawal. For both patients symptoms occurred with lowering of the dosage and persisted for 5 days after complete discontinuation of the drug.

Mutations that affect the ability of the vnd/NK-2 homeoprotein to regulate gene expression: transgenic alterations and tertiary structure.

The importance in downstream target regulation of tertiary structure and DNA binding specificity of the protein encoded by the vndNK-2 homeobox gene is analyzed. The ectopic expression patterns of WT and four mutant vndNK-2 genes are analyzed together with expression of two downstream target genes, ind and msh, which are down-regulated by vndNK-2. Three mutants are deletions of conserved regions (i.

Reduced expression of serotonin receptor(s) in the left colon of patients with colonic inertia.

Purpose: Serotonin regulates colonic motility receptors expressed on neural fibers and smooth muscle. Colonic inertia is characterized by delayed colonic transit. Abnormalities in serotonin receptor protein, as judged by immunoreactivity levels, could contribute to the origin of colonic inertia.

Occlusive wrap dressing reduces infection rate in saphenous vein harvest site.

Background: Infection in the saphenous vein harvest site is a common problem. We developed an occlusive circumferential wrap dressing technique that reduces skin edge tension, eliminates dead space, and prevents external contamination. We compared the surgical site infection rate using the wrap dressing technique with that of standard longitudinal dressings.