Biomedical subjects
Publications and source records attributed to P Sedmera.
New natural cyclosporins were isolated from the mycelium of surface cultivated fungus Tolypocladium terricola. The chemical structures of [Leu4] CS and [MeLeu1] CS = cyclosporin-J, were deduced from the NMR and mass spectral data. Biological activity of new cyclosporins is reported based on the proliferative mitogen stimulation test.
New beauverolides L and La were isolated and identified from the entomopathogenic fungi, Beauveria tenella and Paecilomyces fumosoroseus. Their structures, cyclo-[3-hydroxy-4-methyldecanoyl-L-phenylalanyl-L-alanyl-D-leucyl ], and cyclo-[3-hydroxy-4-methyldecanoyl-L-phenylalanyl-L-alanyl-D-allo-i soleucyl] were deduced from HPLC and GC-mass spectrometric analyses of their hydrolysates and NMR and mass spectral data.
L-[Me-13C]-Methionine, sodium [2-13C]acetate and sodium [1,2-13C]acetate were incorporated into destruxins A, B and E by the entomopathogenic fungus Metarhizium anisopliae. NMR analysis established that methionine is involved in the N-methylation of L-valine and L-alanine, and that one intact acetate unit participates in the biosynthesis of the -CH(OH)-COOH fragment of the hydroxy acid moiety. The presence of two acetate units in proline and isoleucine agrees with the accepted biochemical schemes.
Macrotetrolides isolated from a new producer, Streptomyces globisporus, were identified as nonactin, monactin, dinactin and trinactin. Spectroscopic characterization of these compounds was extended by 13NMR spectra. Chemical ionization with ammonia as reactive gas was proposed for mass-spectroscopic characterization of their mixtures. Their biological activity was confirmed by using larvae of the Colorado potato beetle (Leptinotarsa decemlineata) as a new test model.
Explore the source record for details and available documents.
Alkaline hydrolysis of alpha-D-glucopyranosyl 3,4-anhydro-beta-D-ribo-hexulofuranoside (1) involves participation of HO-2 and leads to 2,3'-anhydrosucrose (2). The structure of 2 was assigned on the basis of the n.m.r. and mass spectra of its hexa-acetate 3 and confirmed by the formation from 2 of the 6,6'-di-(4) and 6,1',6'-tri-O-trityl (5) derivatives, the 4,6-O-isopropylidene derivative (6), and 2,3':3,4-dianhydro-galacto-sucrose, isolated as the tetra-acetate 7. The structure of 7 was confirmed by its conversion into the 4'-O-tosyl-6,1',6'-O-trityl derivative 14 and by unambiguous synthesis from 6.
Semisynthetic derivatives of daunomycinone with 7,9-isopropylacetal, 7-O-methyl, 7-O-(4-penten-2-yl), and 7-O-(2-hydroxyethyl) substituents were converted by Streptomyces peucetius var. caesius (an adriamycin-blocked mutant) into 7-deoxy-13-dihydrodaunomycinone, while daunomycinone was transformed into 13-dihydrodaunomycinone (predominantly) and 7-deoxy-13-dihydrodaunomycinone. S. coeruleorubidus mutants 24-74 (accumulating aclavinone derivatives instead of daunomycin and related compounds) and 96-85 (producing no anthracycline substances), and S. aureofaciens B-96 (a tetracycline-blocked mutant) transformed the above substrates into the corresponding 13-dihydro derivatives, with the exception of 7,9-isopropylacetal daunomycinone which remained intact. 7-O-Propyn-1-yl daunomycinone was not transformed by any of the strains used under the conditions.
Explore the source record for details and available documents.
Isoleucine added to the cultivation medium of Streptomyces cinnamonensis C-100-5 induced a relative increase of the production of monensin B at the expense of monensin A. U-14C-Isoleucine was found not to be a specific monensin B precursor. The incorporation of 1-13C-2-methylbutyrate into monensins A and B showed the label to be evenly incorporated in both products at carbon atoms originating from C(1) of propionate. In regulatory mutants insensitive to 2-amino-3-chlorobutyrate isoleucine influenced the production of monensins only slightly but strains resistant to 2-aminobutyrate and norleucine decreased their total production by 2-12% in the presence of isoleucine which was associated with a decrease of monensin A content by 14-52%. The inhibitory effect of isoleucine on the biosynthesis of valine, a specific precursor of the butyrate unit of monensin A, is discussed.
Explore the source record for details and available documents.
Various blocked mutants were isolated from three leukaemomycin-(daunomycin-)producing strains IMET JA 3933, IMET JA 5142 and IMET JA 5570 of Streptomyces griseus by NTG and UV treatments. Among them, one class of four mutants ZIMET 43707/1P, IMET JA 5570/3P, IMET JA 5570/10P and IMET JA 5142/01P1 produced new blue and red pigments. Two red compounds designated 1PI and 1PII are the main components of the pigment complex produced by culture of the blocked mutant ZIMET 43707/1P. This paper describes the isolation of 1PI and IPII; furthermore, the spectral and physicochemical properties of these anthracyclinones and the elucidation of their structures are reported.
Explore the source record for details and available documents.
By mutagenic treatment and selection procedures the mutant ZIMET 43678 was obtained from a population of the interspecific recombinant Streptomyces violaceus subsp. iremyceticus ZIMET 43615, which showed a changed spectrum of secondary metabolites. The main component isolated from the fermentation broth was a pure anthracycline evidenced by TLC. By means of acid hydrolysis, identification of the degradation products and also by spectroscopic UV/VIS-, IR-, MS-, 1H/13C-NMR- and CD-investigations with intact anthracycline the structure 7-(alpha-L- rhodosaminyl )-beta- rhodomycinon with the absolute configuration 7S, 9R , 10R was found. The anthracycline called beta- rhodomycin -1 (1) exhibits antimicrobial and cytostatic activity in vitro and is also effective on tumour cells in tumour bearing animals.
Explore the source record for details and available documents.
Effect of 44 colchicine derivatives on the induction of antibody response in tissue cultures was tested. Lymphatic cells from the spleen of BALB/c mice were cultivated with antigen (sheep red blood cells) and the number of antibody forming cells was determined by the plaque technique. Most compounds with the immunoinhibitory effect are derived from the colchicine formula (I). The effect was increased by introducing ethyl, formyl or methylenedioxide groups. Colchinols exerted very good immunoinhibitory effect resulting by contraction of tropolone ring C into the aromatic one. A complete loss of the effectivity was detected in the case of glucoside of colchicine, colchiceine, isocolchicine, oxycolchicine, allocolchicine and in lumiderivatives of colchicine. No correlations between the immunoinhibitory effect, toxicity and stathmokinetic effect were detected: decrease of cell viability and arrest of mitoses were not observed in cultured lymphocytes within the range of the immunoinhibitory effect. The effect of colchicine derivatives was manifested as the inhibition of lymphocyte blastogenesis, which is probably the result of membrane transport blockade.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Mutants of Aspergillus niger 194A and 178 requiring lysine differ from the original prototrophic strain K10 and from each other on the course of accumulation of organic acids. In both mutants less citric acid accumulates during the first phase of cultivation but considerably more 2-oxoglutarate and 2-oxoadipate accumulate than in the original strain. Whereas in the 194A mutant this state remains unchanged also during the second phase of cultivation, in the 178 mutant oxo acids are degraded and citric acid is synthesized intensively. The accumulation of 2-oxoglutarate and 2-oxoadipate in the fermentation medium indicates that in A. niger lysine is synthesized via the homocitrate pathway.