Structural requirements for the binding of benzodiazepines to their peripheral-type sites

JK Wang, T Taniguchi and S Spector

The DS19 Friend erythroleukemia cells possess peripheral-type benzodiazepine recognition sites that are similar to those characterized in other tissues and cells. These sites recognize only specific and well-defined ligand structures. In order for the benzodiazepines to bind to these sites, an alkyl group of 3 carbons or less is required at position 1, together with a carbonyl group at position 2. In addition, the binding affinity is enhanced by 4'-halogen or 4'-methoxy substituents, and by 7- or 2'-halogens. However, the affinity is decreased by substitutions at position 3 or 4. Central-type benzodiazepine binding in brain, on the other hand, is not affected by 1-alkyl groups and is inhibited by 4'-substitutions. Furthermore, unlike the peripheral-type site, the brain receptor is stereo- selective. These results demonstrate that the two binding sites are fundamentally different in their recognition of benzodiazepine ligands.

Volume 25, Issue 3, pp. 349-351, 05/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics

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