RP-1776, a novel cyclic peptide, was isolated from the culture broth of Streptomyces sp. KYI 1784. RP-1776 selectively inhibited the binding of PDGF BB to the extracellular domain of the PDGF β-receptor with an IC50 value of 11±6 μM. Detailed binding experiments suggested that RP-1776 directly interacts with PDGF BB. RP-1776 inhibited the phosphorylation of the PDGF β-receptor induced by PDGF BB. These results suggested that RP-1776 antagonizes the signaling of PDGF BB probably through the inhibition of PDGF BB binding to the PDGF β-receptor.
In the course of our screening for inhibitors of sphingosine kinase, we found two active compounds in a culture broth of a fungus, Zopfiella inermis SANK 15183. The structures of the compounds, named S-15183a and b, were elucidated by a combination of spectroscopic analyses to be new azaphilone-type metabolites. S-15183a and b inhibited sphingosine kinase from rat liver with IC50 values of 2.5 and 1.6μM, respectively. S-15183a also inhibited endogenous SPH kinase activity in intact platelets.
A new antibiotic designated TMC-69 has been isolated from, the fermentation broth of a fungal strain Chrysosporium sp. TC 1068. TMC-69 exhibited moderate in vitro cytotoxic activity. TMC-69-6H, a derivative of TMC-69 prepared by hydrogenation, possessed more potent in vitro cytotoxicity than TMC-69, and exhibited in vivo antitumor activity against murine P388 leukemia and B16 melanoma. TMC-69-6H was found to specifically inhibit Cdc25A and B phosphatases.
Four novel cyclic homodecapetide antibiotics, Streptocidins A-D were detected in the mycelium extract of Streptomyces sp. Tü 6071 by HPLC-diode-array and HPLC-electrospraymass-spectrometry screening. The peptides which were closely related in structure to the tyrocidines and gramicidins of Bacillus brevis show antibiotic activities against Gram-positive bacteria.
The structures of the new antibiotics Streptocidins A-D were elucidated as cyclic decapeptides cyclo[L-Val1-L-Orn2-L-Leu3-D-Phe4-L-Pro5-L-Leu6-X7-L-Asn8-L-Gln9-X10] with X7-D-Trp (A, B, C) or D-Phe (D) and X10=L-Tyr (A), L-Trp (B, D), or D-Trp (G). The amino acid composition (including the configuration) of the substances was determined by chiralphase GC-MS of the hydrolysates. The sequences were established by EDMAN degradation following linearisation of the cyclic peptides upon treatment with LiAIH4. NMR spectroscopic studies of Streptocidins C and D confirmed the proposed sequences and provided conformational data which indicate a molecular topology of Streptocidins C and D similar to those of tyrocidine A and gramicidin S.
Two novel antibiotics, TPU-0031-A and B, were isolated from the culture broth of an actinomycete strain. The producing strain, TP-A0556, was identified as Streptomyces sp. based on the taxonomic study. The new antibiotics were obtained by solvent extraction and chromatographic purification. Spectroscopic analyses showed that TPU-0031-A and B were 7'-demethylnovobiocin and 5′′-demethylnovobiocin, respectively. These compounds showed antibiotic activity against Gram-positive and -negative bacteria.
A novel approach to biotransformation is described using a solid medium matrix and Reemay® mesh that gives efficient biotransformation of compounds with minimal matrices in the ensuing gum solids. Using this approach with a newly isolated biotransforming organism, Streptomyces lydicus SX1298, a series of hydroxylations and an O-demethylation is described for selamectin the first endectocide for cats and dogs.
A series of hydrophobia N′-mono and N′, N′′-double alkylated derivatives of the glycopeptide antibiotic eremomycin were synthesized by reductive alkylation after preliminary protection of the N-terminal amino group of the peptide backbone. The investigation of the antibacterial activity in vitro showed that N′-C10H21- and N′-p-(p-chlorophenyl)benzyl derivatives of eremomycin are the most active against vancomycin-resistant enterococci among the compounds obtained though they are less effective than the corresponding lipophilic derivatives of vancomycin. The introduction of two hydrophobic substituents led to a decrease in activity against both susceptible and resistant bacteria. The biochemical evaluation of the mode of action revealed that in addition to binding to D-Ala-D-Ala these compounds also have an alternative mechanism of action that does not require substrate binding.