Selective disruption of protein aggregation by cyclodextrin dimers.
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.
Leung
D K
DK
Department of Chemistry, Columbia University, New York, NY 10027, USA.
Yang
Z
Z
Breslow
R
R
D000243:Adenosine Deaminase / Q000737:chemistry; D058892:Adenosine Deaminase Inhibitors; D001665:Binding Sites; D002950:Citrate (si)-Synthase / Q000037:antagonists & inhibitors / Q000737:chemistry; D003198:Computer Simulation; D003505:Cyclodextrins / Q000737:chemistry* / Q000494:pharmacology*; D019281:Dimerization; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004798:Enzymes / Q000737:chemistry*; D005649:Fumarate Hydratase / Q000037:antagonists & inhibitors / Q000737:chemistry; D005691:Galactose Dehydrogenases / Q000037:antagonists & inhibitors / Q000737:chemistry; D005956:Glucose-6-Phosphate Isomerase / Q000037:antagonists & inhibitors / Q000737:chemistry; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors / Q000737:chemistry; D007064:L-Iditol 2-Dehydrogenase / Q000037:antagonists & inhibitors / Q000737:chemistry; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors / Q000737:chemistry; D046911:Macromolecular Substances; D008958:Models, Molecular; D011487:Protein Conformation
D058892:Adenosine Deaminase Inhibitors; D003505:Cyclodextrins; D004791:Enzyme Inhibitors; D004798:Enzymes; D046911:Macromolecular Substances; D005691:Galactose Dehydrogenases; D007064:L-Iditol 2-Dehydrogenase; D007770:L-Lactate Dehydrogenase; C047959:galactose dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D002950:Citrate (si)-Synthase; D000243:Adenosine Deaminase; D005649:Fumarate Hydratase; D005956:Glucose-6-Phosphate Isomerase