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.