The general formula, proposed earlier for the natural streptothricins E, D, C, B, A and for the biosynthetic streptothricin X was shown to be valid. 1. The presence of a common moiety in streptothricins F, E, D, C, B and A was demonstrated by isolation of N-guan-streptolidyl gulosaminide from preparations of all these antibiotics. 2. It was shown that streptothricins D, C, B, A and X contain unbranched peptide chains, in which residues of β-lysine are linked by their ε-amino groups, whereas β-amino groups are free.
The effect of adriamycin on HeLa S-3 cells grown in monolayers was studied. The growth of HeLa S-3 cells was clearly inhibited at low doses of 0.05 and 0.10 meg/ml. One of the earliest changes of the cells treated with adriamycin was the rapid depression in mitotic frequency. Adriamycin caused inhibition of cell division even when added at the end of DNA synthesis phase. Adriamycin inhibited RNA synthesis more severely than DNA and protein syntheses. Moreover, the specific inhibition of RNA synthesis was observed in logarithmically growing cultures under conditions which permitted normal syntheses of DNA and protein. However, the degree of inhibition of RNA synthesis was reduced in synchronized cultures with excess thymidine. The mode of action of adriamycin is discussed.
An imidazolide (4) obtained from carbobenzoxy-NG=-nitro-L-arginine (3) was reduced with lithium aluminum hydride to give carbobenzoxy-NG=-nitro- L-argininal (5) in good yield. The aldehyde (5) was converted into NG=-nitro-Largininal semicarbazone (7) which was coupled with an active ester of various acylated leucines or isoleucines and then deblocked, giving leupeptins and their analogs, as listed in Table 1. Antiplasmin activities of these compounds are discussed.
Conditions established for viomycin production by Streptomyces griseus var. purpureus in 1-litre flasks were found suitable for production in a 14-litre fermentor, provided that shearing forces were reduced by the use of low initial aeration rates and low agitation rates. The optimum temperature for production was 30°C, no antibiotic being produced at 37°C. 14C-Arginine, and especially 14C-glucose, were satisfactory precursors of 14C-viomycin of moderate specific activity if added 40 hours afer the start of the fermentation. A variety of 14C-amino acids were unsuitable for isotopic labelling since their metabolism led to the release of large amounts of 14CO2. 14C-Acetate also was unsuitable for labelling purposes. Viomycin production was complex, the initial production being associated with sporulation and a secondary production being associated with spore germination and subsequent mycelial growth.
Paromamine (7) and its positional isomer, namely, 6-O-α-D-glucosaminyl-2-deoxystreptamine (8) have been synthesized in satisfactory yields by condensation of racemic mono-O-cyclohexylidene-N, N'-diethoxycarbonyl-2-deoxystreptamine (1) with 3, 4, 6-tri-O-acetyl-N-p-methoxybenzylidene-α-D-glucosaminyl bromide (2). The overall yield of paromamine from 2-deoxystreptamine is 37%.