A simple and rapid method has been developed for the isolation of thermally labile DNA alkylation products. Use of calf thymus DNA in combination with size exclusion filtration provides good yields >40% of chlorambucil-guanine adducts. Application of this method to the isolation of alkylation pr...

An efficient synthesis of the epoxide-containing fragment 4 of carzinophilin has been completed. Intramolecular acyl transfer of a related epoxide afforded amide 16. Comparison by 1H NMR of 4 and 16 with authentic natural product provides further evidence for structural revision of carzinophilin.

The synthetic procedures of the title compound (2), a protected form of carzinophilin (1), were developed. While efforts toward the total synthesis of 1 failed, comparison of the 1H NMR spectra of 2 and some other related compounds with that of 1 provided definite support for the absolute stereo...

The alkylation of d(TAGCTA)2 by an antitumor antibiotic, carzinophilin, and its 4-methyl derivative was investigated. It was found that both carzinophilin (1a) and 4-O-methylcarzinophilin (1b) react with d(TAGCTA)2 to provide the corresponding monoadducts and the interstrand crosslinked adducts....

A model compound bearing the C1–C17 fragment of carzinophilin was synthesized. The synthesis involved coupling reaction of a cyclic thioimidate with the 4H-oxazol-5-one derivative, ring-opening of the 4H-oxazol-5-one to furnish a dehydropeptide system, elaboration of the C1–C6 enolamide, and c...

Synthesis of the model compounds of carzinophilin carrying 2-methylidene-1-aza-bicyclo[3.1.0]hexane systems was achieved. Formation of malonylidenes or N-acyl-glycinylidenepyrrolidines was carried out by utilizing Eschenmoser's sulfide contraction or Herdeis's condensation between the ...

Chemical and biological properties of carzinophilin congeners obtained in the course of our synthetic studies were investigated. These studies revealed feasibility for the use of some analogues as a double alkylating agent. Further, analogues carrying the naphthalene and the epoxide parts were f...

Phosphate strongly repressed the formation of p-aminobenzoic acid (PABA) synthase, an enzyme involved in candicidin biosynthesis. Expression in Streptomyces lividans of the pabS gene (encoding PABA synthase) of Streptomyces griseus is repressed by phosphate at concentrations above 0.1 mM. Howeve...

The requirements for growth and macromolecule synthesis by yeast treated with minimal lethal concentrations of the polyene antibiotic candicidin have been studied. 1.1. Glucose utilization, but not protein synthesis or growth, was protected by preincubation of cells with cofactors required for g...

The antifungal polyene antibiotic candicidin isolated from soil actinomyces is produced by Streptomyces sp. It is one of many macrocyclic ring compounds which display potent antifungal properties with no apparent antibacterial activity. These antibiotics are characterized by the possession of a ...

Cerulenin, an inhibitor of fatty acid synthesis, inhibits specifically the biosynthesis of the polyene macrolide candicidin by resting cells of Streptomyces griseus. 50% inhibition was achieved with a cerulenin concentration of 1.5 μg/ml. Cells in which candicidin synthesis was inhibited for 10...

SummaryOn studying the production of candicidin by Streptomyces griseus, certain factors controlling the biosynthesis of the antibiotic were explored. The antibiotic was produced at 72 hours of the incubation period. Glucose, mannose, sucrose, and molasses were the best carbon sources for the pr...

The action of the polyene antibiotic candicidin (a heptaene) on yeast cells in growth medium has been studied. Candicidin at the growth-inhibiting concentration produced the following sequence of events. (1) There was an immediate and rapid loss of K+. (2) After about 10 min, Mg2+ was lost to th...

In a double-blind study, candicidin therapy resulted in over-all clinical improvement of benign prostatec hypertrophy symptoms in 78.1 per cent of treated patients compared with 10 per cent for patients given a placebo. Histologic review of prostates of candicidin-treated patients showed more st...

The complete gene cluster for biosynthesis of a polyene complex, FR-008, spans 137.2 kb of the genome of Streptomyces sp. FR-008 consisting of six genes for a modular PKS and 15 additional genes. The extensive similarity to the partially characterized candicidin gene cluster in Streptomyces gris...

An International Reference Preparation of Candicidin has been established, the potency of which was estimated from the results of a collaborative assay carried out by five laboratories in four countries. Variations in the results resulted from the heterogeneous nature of the antibiotic and the d...

Medium compositions for the production of the novel derivatives of FR-008/Candicidin which was produced by a mutant of Streptomyces sp. FR-008 were optimized using two statistical methods including Plackett–Burman design (P–B), which was applied to find the key ingredients for the best medium ...

The antifungal activity of ascosin is suppressed by the presence of certain unsaturated fatty acids such as oleic, linoleic, and linolenic acids, while the saturated, straight-chain fatty acids studied did not show such action. The antifungal action is also suppressed by Tween 80 and to a lesser...

In a previous report it has been shown that the antibiotic ascosin inhibits the cytochrome linked electron transport system at the same site as does antimycin. This antimycin sensitive site lies between coenzyme Q or cytochrome b and cytochrome c1. Both antimycin and ascosin exhibit no antibacte...

Ascosin, a heptaene antibiotic produced by Streptomyces canescus (NRRL 2419) which inhibited yeast respiration completely, had no effect on glycolysis. Ascosin did not inhibit the reduction of the dye, 2,6-dichlorophenol indophenol with succinate as the substrate. Nor did it inhibit the oxidatio...