Enantioselectivity of the binding of (S)- and (R)-7-chloro-1,3-dihydro-3-methyl-5-phenyl-2H-1,4-benzodiazepines to human serum albumin.
By combining the gel filtration and circular dichroism (CD) methods in studying the binding of chiral (S)/(R)-(I) to human serum albumin (HSA) the following results were obtained: HSA affinity for (S)-(I) is about 17 times higher than for (R)-(I); there exist two independent and nonequivalent binding sites for (S)-(I), and one site of lower affinity for (R)-(I); at equimolar concentrations of (I) and HSA, (S)-enantiomer is bound up to 45%, but (R)-enantiomer binds up to 22% only; differential CD-spectra at various concentrations, in the presence of HSA at 1.45 X 10(-5) M concentration, reveals distortions of the chromophoric system i.e. of the conformation of (S)-(I). This effect, and the low affinity of both enantiomers for HSA, allows only a qualitative interpretation of CD-data.
Gratton
G
G
Decorte
E
E
Moimas
F
F
Angeli
C
C
Sunjić
V
V
D001569:Benzodiazepines / Q000097:blood / Q000378:metabolism*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002850:Chromatography, Gel; D002942:Circular Dichroism; D006801:Humans; D011485:Protein Binding; D011963:Receptors, GABA-A / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D011963:Receptors, GABA-A; D012709:Serum Albumin; D001569:Benzodiazepines