Robert T. Goegelman

Avermectins, New Family of Potent Anthelmintic Agents: Isolation and Chromatographic Properties

The avermectins, a family of new anthelmintic agents, were isolated from the mycelia of Streptomyces avermitilis. Four closely related major components and four homologous minor components were separated from the complex. Solvent extraction, solvent partition, and adsorption methods were used to isolate and purify the complex; novel partition chromatography systems using Sephadex LH-20 were used to separate the components. A reverse-phase high-pressure liquid chromatography assay for the quantitative determination of all components was used extensively to monitor the purification methods.

Cephamycins, a New Family of β-Lactam Antibiotics II. Isolation and Chemical Characterization

Cephamycins A and B were isolated from the same fermentation broth of various actinomycetes by adsorption and ion-exchange methods. The antibiotics were separated from each other by column chromatography on a dextran-based ion-exchange resin. Cephamycin C was isolated from a different fermentation broth by ion-exchange and gel-filtration methods. The chemical characteristics of these new antibiotics were determined.

[3H]paraherquamide binding to Caenorhabditis elegans : studies on a potent new anthelmintic agent

Paraherquamide was identified recently as a potent anthelmintic agent. In this paper we describe the identification and characterization of a specific, high-affinity paraherquamide binding site in a membrane preparation isolated from the free-living nematode, Caenorhabditis elegans. [3H] Paraherquamide bound specifically to C. elegans membranes with an apparent dissociation constant, Kd, of 263 nM. A series of paraherquamide analogs were examined, and their relative affinity for the paraherquamide binding site correlated with their nematocidal activity. Phenothiazines were the only other class of anthelmintics tested which inhibited specific [3H]paraherquamide binding. These results suggest that the anthelmintic activity of paraherquamide and phenothiazine is mediated via an interaction with a common binding site.

STUDIES ON THE AVERMECTIN FERMENTATION

ABSTRACT The avermectins are a group of potent anthelmintic and insecticide active compounds produced by Streptomyces avermitilis. Synthesis of the avermectins in complex medium is regulated by added carbon, nitrogen, phosphorous and sulfur. The antifoam polyglycol P-2000 also influences the fermentation. The yield of nonproducing bald isolates is increased from 2% to as much as 60% by treatment with intercalating dyes. The possible involvement of extrachromosomal elements in controlling aerial mycelia, pigment and avermectin production is suggested.