Abstract
A new ryanodine-binding inhibitor, verticilide, was isolated from the cultured broth of a fungus, Verticillium sp. FKI-1033. It is a 24-membered ring cyclic depsipeptide, its structure being elucidated as cyclo[(2R)-2-hydroxyheptanoyl-N-methyl- L-alanyl](4). Verticilide inhibited ryanodine binding to ryanodine receptors in the cockroach at an IC(50) value of 4.2 microM, whereas inhibition against mouse ryanodine receptors was weak (IC(50)=53.9 microM).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Membrane / metabolism
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Cockroaches
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Depsipeptides / chemistry
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Depsipeptides / metabolism*
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Depsipeptides / pharmacology*
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Mice
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Molecular Biology
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Muscle Fibers, Skeletal / metabolism
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Protein Binding
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Ryanodine / antagonists & inhibitors*
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Ryanodine Receptor Calcium Release Channel / metabolism*
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Structure-Activity Relationship
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Verticillium / metabolism*
Substances
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Depsipeptides
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Ryanodine Receptor Calcium Release Channel
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verticilide
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Ryanodine