ABSTRACT
An antimetabolite, THX, was isolated from fermentation broths of the thienamycin producer, Streptomyces cattleya, when the organism was grown in the presence of a fluorine-containing substrate. THX was subsequently identified as one of the four possible stereoisomers of 4-fluorothreonine. Inorganic fluoride or any one of a number of organofluorine compounds can be used as precursors of 4-fluorothreonine. In addition, 19F NMR has provided evidence that the organism synthesizes fluoroacetate under the same fermentation conditions. The in vitro antibacterial spectrum of 4-fluorothreonine is also presented.
Subject(s)
Anti-Bacterial Agents/isolation & purification , Antimetabolites/isolation & purification , Fluoroacetates/metabolism , Streptomyces/metabolism , Thienamycins/biosynthesis , Threonine/analogs & derivatives , Animals , Anti-Bacterial Agents/pharmacology , Antimetabolites/pharmacology , Bacterial Infections/drug therapy , Magnetic Resonance Spectroscopy , Mice , Pseudomonas aeruginosa/drug effects , Stereoisomerism , Threonine/biosynthesis , Threonine/pharmacologySubject(s)
Anti-Bacterial Agents/isolation & purification , Antimetabolites/isolation & purification , Serine/analogs & derivatives , Streptomyces/metabolism , Threonine/antagonists & inhibitors , Animals , Anti-Bacterial Agents/pharmacology , Antimetabolites/pharmacology , Chemical Phenomena , Chemistry , Chickens , Magnetic Resonance Spectroscopy , Pseudomonas aeruginosa/drug effects , Serine/isolation & purification , Serine/pharmacologyABSTRACT
A material having antibradykinin activity on isolated guinea pig ileum was partially purified from the nondialysate of the pulp of Aloe saponaria by repetition of gel chromatography using a hydrophilic polyvinyl gel and dextran gels. From the results of amino acid and carbohydrate analyses, the antibradykinin-active material was estimated to be a glycoprotein. It was found that this material catalyzes the hydrolysis of bradykinin at pH 7.4. The results of peptide analysis using reversed-phase high-performance liquid chromatography coupled with amino acid analysis indicate that this glycoprotein cleaves the Gly4-Phe5 and Pro7-Phe8 bonds of the bradykinin molecule.
Subject(s)
Aloe/analysis , Bradykinin/antagonists & inhibitors , Plants, Medicinal/analysis , Amino Acids/analysis , Animals , Chemical Phenomena , Chemistry , Guinea Pigs , Ileum/drug effects , In Vitro Techniques , Muscle Contraction/drug effects , Muscle, Smooth/drug effectsSubject(s)
Aloe , Cardiotonic Agents/isolation & purification , Plant Extracts/pharmacology , Plants, Medicinal , Animals , Guinea Pigs , In Vitro Techniques , Rabbits , RatsABSTRACT
The relaxing effect and possible mechanism of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) on isolated rabbit artery were investigated. The addition of W-7 in concentrations ranging from 1 X 10(-6) to 3 X 10(-4) M caused a significant relaxation of isolated rabbit vascular strips contracted by KCl, prostaglandin F2alpha, norepinephrine, histamine, CaCl2, serotonin or angiotensin II. W-7 also caused a shift to the right of the dose-response curves for all agonists tested. Propranolol and atropine did not affect W-7 induced relaxation, suggesting that this drug does not act through beta adrenergic or cholinergic receptors. Superprecipitation of actomyosin from bovine aorta smooth muscle was inhibited by the addition of W-7 in a dose-dependent fashion. The concentration of W-7 which inhibited superprecipitation of bovine aorta smooth muscle actomyosin was in good agreement with the dose producing relaxation of isolated vascular strips. These facts suggest that W-7 produces relaxation of isolated vascular strips by inhibiting actin and myosin interaction.
