Enzymes in the respiratory chain are increasingly seen as potential targets against multi-drug resistance of human pathogens and cancerous cells. However, a detailed understanding of the mechanism and specificity determinants of known inhibitors is still lacking. Oligomycin, for example, has bee...
The enantiospecific synthesis of the oligomycin B degradation product 2, corresponding to the C19–C34 spiroketal portion, has been achieved by sequential coupling of the C19–C21, C22–C27, and C28–C34 subunits, establishing the absolute stereochemistry of oligomycin B.
Ciguatoxins (CTXs) produced by benthic Gambierdiscus dinoflagellates, readily biotransform and bioaccumulate in food chains ultimately bioconcentrating in high-order, carnivorous marine species. Certain shark species, often feeding at, or near the top of the food-chain have the ability to bioacc...
The electronic structure, bonding, and optical properties of six polymorphs of SiC: 3C, 2H, 4H, 6H, 15R, and 21R were studied by the density functional-based first-principles OLCAO method. The results were compared with other existing calculations as well as experimental data. It is shown that t...
ObjectiveInterleukin (IL)-21, a member of the IL-2 family, has antitumor activity and is now being tested in non-Hodgkin's lymphoma in combination with anti-CD20 antibodies. IL-21 may either induce apoptosis or promote growth in different lymphoid malignancies. We therefore investigated the...
The formation, densification behaviour and mechanical properties of 21R AlN-polytypoid(SiAl6O2N6) were studied. The results show that 12H(SiAl5O2N5) is a transitional phase during the formation of 21R. The additives Sm2O3 and Nd2O3, especially combined with Al2O3 can effectively promote the dens...
To determine the potential role of interleukin-21 (IL-21) / IL-21 receptor (IL-21R) in the pathogenesis of autoimmune thyroid disease (AITD) mainly known as Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). IL-21 and IL-21R of peripheral blood samples and/or thyroid tissues from AITD pati...
Interleukin-21 (IL-21) is a T cell-derived cytokine modulating T cell, B cell, and natural killer cell responses. To determine whether IL-21 contributes to pathologic processes, recombinant IL-21 receptor (R) fusion protein (rhIL-21R-Fc) was examined in mice models of autoimmune arthritis (colla...
The current study investigated the therapeutic effect of berberine (BBR), an alkaloid derivative against IL-21/IL-21R mediated phosphotidyl inositol 3 kinase/protein kinase B (PI3K/Akt) signaling in adjuvant induced arthritic fibroblast-like synoviocytes (AA-FLS) isolated from rats and IL-21 med...
T helper cells 17 (Th17) are recognized as key participants in the pathogenesis of chronic autoimmune diseases such as multiple sclerosis (MS). Regulation of Th17 differentiation is a valuable strategy for diagnosis and treatment of these complicated immune disorders. Here, by genome-wide expres...
Information is limited regarding sources, distribution, environmental behavior, and fate of prescribed and illicit drugs. Wastewater treatment plant (WWTP) effluents can be one of the sources of pharmaceutical and personal care products (PPCP) into streams, rivers and lakes. The objective of thi...
The sequence specificity of the pluramycin antibiotics hedamycin and DC92-B, was established in intact human cells using a linear amplification system. In this system an oligonucleotide primer is extended by Taq DNA polymerase up to a damage site. The products are run on a DNA sequencing gel and...
The interaction of hedamycin with covalently closed circular PM-2 DNA was examined. Hedamycin produced strand breakage detectable in alkaline sucrose gradients. Under neutral conditions hedamycin inhibited ethidium bromide binding and induced conformational changes in PM-2 DNA.
1. The interaction of hedamycin, an antibiotic from Streptomyces griseoruber with polynucleotides and the effect of this interaction on their template capacity in nucleic acid synthesis have been studied. A peak at 430 mμ in the spectrum of hedamycin is depressed and shifted to higher wave leng...
The 13C NMR spectra of hedamycin, kidamycin and some of their derivatives have been fully assigned. Proton coupling constants and 13C NMR acetylation shifts indicate that the conformations of the highly substituted tetrahydropyran rings in solution are chair forms for ring E, as well as for ring...
Covalent binding of the antitumour antibiotic hedamycin to the self-complementary hexadeoxyribonucleotide 5′-CACGTG-3′ has been investigated by electrospray ionization mass spectrometry (ESI-MS). Ions due to double-stranded forms of the free 5′-CACGTG-3′ and the hedamycin-5′-CACGTG-3′ addu...
The sequence selectivity of DNA alkylation by the recently isolated pluramycin antitumour antibiotic DC92-B has been investigated using two methods: a piperidine-induced strand-breaking procedure and a Taq DNA polymerase/linear amplification method. These techniques reveal that guanines are the ...
Background: The pluramycins are a class of antitumor antibiotics that exert their biological activity through interaction with DNA. Recent studies with the analog altromycin B have determined that these agents intercalate into the DNA molecule, position carbohydrate substituents into both major ...
A detailed spectral comparison between kidamycin 1 and hedamycin 13 shows that the two antibiotics have almost identical structures. However, the olefinic side chain at C-2 of kidamycin is replaced in hedamycin by a 2,3,4,5-diepoxy-2-hexyl group.
The biosynthetic gene cluster for the pluramycin-type antitumor antibiotic hedamycin has been cloned from Streptomyces griseoruber. Sequence analysis of the 45.6 kb region revealed a variety of unique features such as a fabH homolog (KSIII), an acyltransferase (AT) gene, a set of type I polyketi...
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