Abstract
[structure: see text] The lobatamides and related salicylate enamide natural products are potent mammalian V-ATPase inhibitors. To probe details of binding of the lobatamides to mammalian V-ATPase, three photoactivatable analogues bearing benzophenone photoaffinity labels have been prepared. The analogues were designed on the basis of a simplified acyclic analogue 2. Late-stage installation of the enamide side chain and tandem deallylation/amidation were employed in synthetic routes to these derivatives. Simplified analogue 2 showed strong inhibition against bovine clathrin-coated vesicle V-ATPase (10 nM). Analogues 3-5 were also evaluated for inhibition of bovine V-ATPase in order to select a suitable candidate for future photoaffinity labeling studies.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Binding Sites
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Catalysis
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Cattle
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Enzyme Inhibitors* / analysis
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Enzyme Inhibitors* / chemical synthesis
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Enzyme Inhibitors* / chemistry
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Enzyme Inhibitors* / pharmacology
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Indicators and Reagents
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Inhibitory Concentration 50
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Macrolides* / analysis
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Macrolides* / chemical synthesis
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Macrolides* / chemistry
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Macrolides* / pharmacology
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Molecular Structure
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Photochemistry
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Salicylates* / analysis
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Salicylates* / chemical synthesis
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Salicylates* / chemistry
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Salicylates* / pharmacology
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Structure-Activity Relationship
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Vacuolar Proton-Translocating ATPases / antagonists & inhibitors
Substances
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Enzyme Inhibitors
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Indicators and Reagents
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Macrolides
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Salicylates
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lobatamide C
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Vacuolar Proton-Translocating ATPases