Aspergillus deflectus CBS 109.55 when grown on an iron-free medium produces several antibiotics; one of these was isolated and identified as desferritriacetylfusigen. It inhibits the growth of bacteria, whereas yeasts and fungi are not or only weakly affected.
Very recently, 1-N-methyl-Ψ-uridine was isolated from the culture filtrate of Streptomyces platensis var. clarensis along with an antibacterial and antiviral antibiotic, U-44590. We achieved chemical syntheses of 1-N-methyl-Ψ -uridine by selective methylation of Ψ-uridine in two different routes and established the identity of the synthetic nucleoside with the natural product.
Minosaminomycin is structurally related to kasugamycin and inhibits protein synthesis in mycobacteria. It also inhibits phage f2 RNA-directed protein synthesis in a cell-free system of Escherichia coliby 50% at 2×10-7M. It is 100-times more potent than kasugamycin in this system. At 10-7M minosaminomycin inhibits EF-T dependent binding of aminoacyl-tRNA to ribosomes by 50%. This effect is markedly diminished if minosaminomycin is added to the assay say system after a brief incubation of ribosomes with mRNA. Like kasugamycin, minosa- minomycin preferentially inhibits the initiation of protein synthesis directed by phage f2 RNA in vitroand does not cause miscoding. Ribosomes from kasugamycin-resistant mutants Ksg A and Ksg C were as sensitive to minosaminomycin as those from each parent strain. In spite of the strong inhibitory activity of minosaminomycin manifested in cell-free systems ofE. coli, this compound inhibits the growth of the organism itself only slightly. This discrepancy could be ascribed to impermeability, asE. colicells with modified permeability show greater sensitivity sitivity to minosaminomycin. There is no indication that the antibiotic is inactivated inE. coli cells. On the basis of these results, the structural features of these antibiotics essential for interaction with ribosomes and for permeability into the cells are discussed.
Reduction of virginiamycin S with sodium borohydride produces allo- and normal-dihydro-virginiamycin S. Reduction of the tosylhydrazone of virginiamycin S with sodium cyanoboro-hydride affords deoxyvirginiamycin S. These compounds are less active than virginiamycin S. Like virginiamycin S they enhance the activity of virginiamycin M1.
A structure is assigned to the tetraene antibiotic rimocidin, based in part on 13C NMR spectroscopy and field desorption mass spectrometry. The structure assigned revises a structure proposed in 1966 which was anomalous in relation to those of other polyene antibiotics.
An improved general method for the preparation of methyl esters of polyene antibiotics is discussed. Using this method methyl esters of pimaricin, nystatin, eurocidin, hamycin, hamycins A and B, aureofungin, partricins A and B, candimycin, candicidin, and amphotericin B have been prepared and their physical properties are reported. The biological activities of hamycins A and B and their methyl esters are also described.
The addition of bleomycin to a nuclear incorporating system results in an increased incorporation of 3H-thymidine 5'-triphosphate (3H-TTP) into the DNA of liver and hepatoma nuclei. Bleomycin added to the nuclear incorporating system also produces scissions of DNA as determined by sucrose density gradient centrifugation of the extracted DNA. The action of bleomycin is dependent on the presence of sulfhydryl agents in the incubation mixture. Two compounds, N-ethyl maleimide and daunomycin, inhibit the bleomycin-induced incorporation of 3H-TTP preferentially. N-Ethyl maleimide inhibits bleomycin-induced activity in liver and hepatoma 7777 nuclei equally. Lower levels of daunomycin inhibit the bleomycin-induced activity in the hepatoma 7777 nuclei than are required to inhibit the activity in liver nuclei. The two compounds inhibit the bleomycin effect by different mechanisms. The addition of N-ethyl maleimide to bleomycin in the incubation system prevents bleomycin from causing breaks in the DNA. The addition of daunomycin, despite inhibition of bleomycin-induced 3H-TTP incorporation, does not affect the bleomycin-produced breaks in the DNA. N-Ethyl maleimide acts by binding to the DNA and by competing with a sulfhydryl agent for bleomycin-sensitive sites on the DNA. Daunomycin apparently inhibits a repair enzyme that is responsible for the increased incorporation following bleomycin treatment.