A novel complex of isotetracenone (angucyclinone) group antibiotics was discovered from the cultured broth of Streptomyces griseorubiginosus No. Q144-2. The antibiotic consisted of six related factors, designated rubiginones A1? A2, B^B2, Cx and C2. They significantly potentiated cytotoxicity of vincristine (VCR) against VCR-resistant P388 leukemia and Moser cells.
A newstrain of Microtetraspora parvosata subsp. kistnae subsp. nov. (ATCC55076) was found to produce newantiviral antibiotics, designated kistamicins A and B. These antibiotics exhibited activity against influenza virus type A and moderate activity against Gram-positive bacteria.Chemoprevention of viruses causing mammalian diseases is becoming more and more important. In our continuing search for novel antiviral activities from microbial metabolites, a new actinomycete strain No. S382-8 isolated from a soil sample collected near the Kistna River in Andhra Pradesh State, India, was found to produce new antiviral antibiotics, designated kistamicins A and B (formerly called BU-4344V). These have potent activity against influenza virus type A Victoria strain in infected Madin Darby canine kidney (MDCK) cells by cytopathic effect reduction assay. They also showed antimicrobial activity against Gram-positive bacteria. This paper reports the taxonomy of the producing organism and the fermentation, isolation, physico-chemical properties and biological activities of kistamicins A and B. The structure determination will be described in the following paper1}.
Taxonomic Studies
MorphologyThe substrate mycelium is well-branched and non-fragmenting (0.5 fim in diameter). Aerial mycelium is poorly formed on a limited number of media and bears monopodially branched chains of spores. The spore chain are short (10 to 20 spores per chain), mostly sessile with hooks or tightly closed spirals at the tip. Some tightly closed spirals are observed as pseudosporangia. The spores are spherical or oblong (0.7~0.9 x 0.8~1.5/mi), non-motile, and have a smooth surface.Cultural and Physiological Characteristics2'3) The substrate mycelia is colorless, brownish pink to deep red. The aerial mycelium, if formed, is white. Melanoid and other distinct diffusible pigments are not formed. The temperature range for growth is 22°C to 45°C. Strain No. S328-8 grows on 3%but not 4%NaCl. It is sensitive to lysozyme. The cultural and physiological characteristics of strain No. S382-8 are shown in Tables 1 and 2, respectively.
ChemotaxonomyWhole cell hydrolysate contains m^o-diaminopimelic acid, ribose, madurose, mannose, galactose,
Wehave recently discovered a complex of new isotetracenone group antibiotics, rubiginones, in our screening for vincristine (VCR)-induced cytotoxicity potentiators1*. In the continuation of the screening program, an actinomycete strain Q576-2 identified as Streptoverticillium aspergilloides, was found to produce a new active substance. Isolation and chemical studies of the responsible substance
We characterized the structure of human endogenous retroviral env RNA transcripts by Northern blot hybridization and cDNA cloning. Polyadenylated 3.0and 1.7-kilobase env RNAs can be identified in placenta, colon carcinoma, and breast carcinoma cells. We have obtained partial cDNA clones of both size classes of RNAs. Both env RNAs contained putative gp7O coding sequences; the 1.7-kilobase species, however, lacked sequences in the 3' env region which could specify a pl5E analog. Both cDNA clones contained in-frame termination codons; thus, neither could encode full-length env proteins.
Antibodies were raised against the sequence Glu-Glu-Glu-Glu-Tyr-Met-Pro-Met-Glu, which represents a part of the middle T antigen of polyomavirus that is considered to be important in inducing the phenotype of transformed cells. The antibodies reacted with native as well as denatured middle T antigens. In addition, the antibodies immunoprecipitated a cellular protein with an apparent molecular weight of 130,000 (130K) from mouse and rat cells. In some cases, a 33K protein was also immunoprecipitated. Immunoprecipitation of middle T antigen as well as 130K and 33K proteins was blocked by the peptide. The antibodies labeled microfilaments of untransformed mouse, rat, human, and chicken cells by immunofluorescence. This labeling was also blocked by the peptide. The labeling pattern and distribution under a variety of conditions were indistinguishable from those of anti-actin antibodies, although no evidence has been obtained to indicate that the anti-peptide antibodies react with actin. The 130K protein migrated in sodium dodecyl sulfate-polyacrylamide gel electrophoresis slightly slower than chicken gizzard vinculin (130K) and slightly faster than myosin light-chain kinase of chicken smooth muscle (130K). Neither of these proteins absorbed the antipeptide antibodies. The 33K protein does not seem to be tropomyosin (32K to 40K). The early region of polyomavirus encodes three proteins in an overlapping manner. They are commonly called large, middle, and small T antigens (12, 16, 22, 55). Middle T antigen is a main inducer of the phenotype of transformed cells (24), and without it transformation does not occur. Middle T antigen alone can transform established lines of cells (54), although large and possibly small T antigens may also be required for the full expression of the phenotype of transformation in low amounts of mitogenic growth factors in culture medium (40). Large or small T antigens alone cannot transform cells (5, 26, 40, 45). Middle T antigen has a molecular weight of 49,000 (49K) and migrates in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) as a 55K to 60K protein (20, 23, 44). The amino-terminal half of middle T antigen is almost completely homologous to small T antigen. The carboxyl-terminal half of middle T antigen is the unique region, a large part of which is encoded in a region of the viral genome
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