Anantin--a peptide antagonist of the atrial natriuretic factor (ANF). I. Producing organism, fermentation, isolation and biological activity.
Anantin, a peptide binding to the receptor of the atrial natriuretic factor (ANF) was isolated from a strain of Streptomyces coerulescens. The molecule consists of 17 natural L-amino acids which form a peptidic ring system. It has a MW of 1,871.0. The chemical composition is C90H111N21O24. The compound was found to bind competitively to ANF-receptors from bovine adrenal cortex (Kd = 0.61 microM). Furthermore, it dose-dependently inhibited the ANF-induced intracellular cyclic guanosine monophosphate accumulation in bovine aorta smooth muscle cells. At the same concentration no agonistic effects were detectable in these cells. Thus, anantin is considered to be the first microbially produced antagonist of the cardiac hormone, ANF.
Weber
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Pharma Research Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Fischli
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Hochuli
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Kupfer
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Weibel
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EK
D000302:Adrenal Cortex / Q000378:metabolism; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors*; D001667:Binding, Competitive; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D006152:Cyclic GMP / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004952:Esters; D005285:Fermentation; D013058:Mass Spectrometry; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012988:Soil Microbiology; D013055:Spectrophotometry, Infrared; D013302:Streptomyces / Q000378:metabolism*
D000596:Amino Acids; D004952:Esters; D010456:Peptides, Cyclic; D011956:Receptors, Cell Surface; C068090:anantin; C068091:des-phenylalanine-anantin; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP