Abstract
Beta-cyclodextrin (CD) dimers (n = 11) were synthesized and tested against eight enzymes, seven of which were dimeric or tetrameric, for inhibitor activity. Initial screening showed that only L-lactate dehydrogenase and citrate synthase were inhibited but only by two specific CD dimers in which two beta-CDs were linked on the secondary face by a pyridine-2,6-dicarboxylic group. Further investigation suggested that these CD dimers inhibit the activity of L-lactate dehydrogenase and citrate synthase at least in part by disruption of protein-protein aggregation.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenosine Deaminase / chemistry
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Adenosine Deaminase Inhibitors
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Binding Sites
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Citrate (si)-Synthase / antagonists & inhibitors
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Citrate (si)-Synthase / chemistry
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Computer Simulation
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Cyclodextrins / chemistry*
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Cyclodextrins / pharmacology*
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Dimerization
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Enzymes / chemistry*
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Fumarate Hydratase / antagonists & inhibitors
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Fumarate Hydratase / chemistry
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Galactose Dehydrogenases / antagonists & inhibitors
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Galactose Dehydrogenases / chemistry
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Glucose-6-Phosphate Isomerase / antagonists & inhibitors
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Glucose-6-Phosphate Isomerase / chemistry
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Glucosephosphate Dehydrogenase / antagonists & inhibitors
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Glucosephosphate Dehydrogenase / chemistry
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L-Iditol 2-Dehydrogenase / antagonists & inhibitors
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L-Iditol 2-Dehydrogenase / chemistry
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L-Lactate Dehydrogenase / antagonists & inhibitors
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L-Lactate Dehydrogenase / chemistry
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Macromolecular Substances
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Models, Molecular
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Protein Conformation
Substances
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Adenosine Deaminase Inhibitors
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Cyclodextrins
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Enzyme Inhibitors
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Enzymes
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Macromolecular Substances
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Galactose Dehydrogenases
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L-Iditol 2-Dehydrogenase
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L-Lactate Dehydrogenase
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galactose dehydrogenase
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Glucosephosphate Dehydrogenase
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Citrate (si)-Synthase
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Adenosine Deaminase
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Fumarate Hydratase
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Glucose-6-Phosphate Isomerase