Novel and potent gastrin and brain cholecystokinin antagonists from Streptomyces olivaceus. Taxonomy, fermentation, isolation, chemical conversions, and physico-chemical and biochemical properties
| Autor: | H. Boyd Woodruff, Kristine A. Faust, Deborah L. Zink, Sara A. Currie, George M. Garrity, Raymond S.L. Chang, Debra Bogen, Otto D. Hensens, Magda M. Gagliardi, Loretta Zitano, Cheryl D. Schwartz, Y. K. Tony Lam |
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| Rok vydání: | 1991 |
| Předmět: |
Male
Magnetic Resonance Spectroscopy Guinea Pigs Neuropeptide Binding Competitive Virginiamycin digestive system Gastrins Drug Discovery medicine Animals Pancreas Chromatography High Pressure Liquid Gastrin Cholecystokinin Pharmacology Bacteria biology Streptomycetaceae digestive oral and skin physiology Brain biology.organism_classification Streptomyces Rats Liver Biochemistry Gastrointestinal hormone Gastric Mucosa Fermentation Receptors Cholecystokinin Epimer Actinomycetales hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | The Journal of Antibiotics. 44:613-625 |
| ISSN: | 1881-1469 0021-8820 |
| DOI: | 10.7164/antibiotics.44.613 |
| Popis: | The discovery and physico-chemical characterization of three novel and minor virginiamycin M1 analogs as potent gastrin antagonists from a culture of a strain of Streptomyces olivaceus are described. These analogs are L-156,586, L-156,587 and L-156,588. They are, respectively, 15-dihydro-13,14-anhydro-, 13,14-anhydro- and 13-desoxy-analogs of virginiamycin M1. We also chemically converted virginiamycin M1 (via L-156,587) to L-156,586 and its unnatural epimer, L-156,906. These analogs are competitive and selective antagonists of gastrin and brain cholecystokinin binding at nanomolar concentrations. These are the most potent gastrin/brain cholecystokinin antagonists from natural products. The same compounds showed poor Gram-positive antibiotic activity versus virginiamycin M1. Structurally related Gram-positive antibiotics, griseoviridin and madumycin I, were inactive in gastrin and brain cholecystokinin binding at up to 100 microM. |
| Databáze: | OpenAIRE |
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