CIRCULAR-DICHROISM AND GEL-FILTRATION STUDY OF BINDING OF PROCHIRAL AND CHIRAL 1,4-BENZODIAZEPIN-2-ONES TO HUMAN-SERUM ALBUMIN

Combining circular dichroism (c.d.) and gel filtration method in studying the binding of chiral ((S)/R)-1) and prochiral (2. diazepam and 3. desmethyldiazepam) benzodiazepines to human serum albumin (HSA), the following results were obtained: c.d. measurements revealed that both enantiomers of 1 are bound by HSA with different affinities. Gel filtration measurements revealed the following data on binding; (a) the HSA affinity for (S)-1 is about 40 times higher than for (R)-1, (b) for (S)-1 exist two independent and nonequivalent sites of high affinity and for (R)-1 two independent equivalent sites of low affinity, (c) at equimolar concentrations of 1 and HSA, (S)-enantiomer is bound up to 5 3 per cent, but (R)-enantiomer up to 18 per cent only; at the same ratio of ligand to protein prochiral 3 was bound up to 56 per cent. © 1979.