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Stereoselective Binding of the Enantiomers of Four Closely Related N ‐Methyl‐Barbiturates to Human, Bovine, and Rat Serum Albumin
Author(s) -
Büch Horst Paul,
Krug Regina,
Knabe Joachim
Publication year - 1996
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19963290805
Subject(s) - enantiomer , chemistry , albumin , bovine serum albumin , serum albumin , stereoselectivity , stereochemistry , binding site , chromatography , biochemistry , catalysis
Albumin binding for the enantiomers of four closely related N ‐methyl‐5‐phenyl‐5‐alkyl‐barbiturates 1–4 was investigated for three different mammalian species by means of equilibrium dialysis. Lipid solubility ( n ‐heptane/phosphate buffer distribution coefficient) increased stepwise by a factor of 56 from 1 to 4. Bovine serum albumin: The ( S )‐(+)‐enantiomers of 1–4 were bound in a higher percentage than the ( R )‐(−)‐enantiomers; lengthening of the aliphatic side‐chain increased the binding extent in both enantiomeric groups. Human serum albumin: Binding of ( S )‐(+)‐ 1 and ( S )‐(+)‐ 4 was higher than that of the ( R )‐(−)‐enantiomers; with ( S )‐(+)‐ 2 and ( S )‐(+)‐ 3 it was much lower than that of the corresponding ( R )‐(−)‐enantiomers. Lengthening of the aliphatic side chain increased the binding extent of the ( S )‐(+)‐ as well as of the ( R )‐(−)‐enantiomers, but with two exceptions: 1. The ( S )‐(+)‐ 1 binding exceeded that of the ( S )‐(+)‐ 2 by a factor of nearly two 2. The binding extent of ( R )‐(−)‐ 4 was not further increased in comparison to ( R )‐(−)‐ 3. Rat serum albumin: ( S )‐(+)‐ 1 and ( S )‐(+)‐ 2 were bound in a lower percentage than the ( R )‐(−)‐enantiomers, both 3 ‐enantiomers showing an equal binding extent; ( S )‐(+)‐ 4 was bound to a slightly greater extent than the ( R )‐(−)‐ 4. In the group of the ( S )‐(+)‐enantiomers, the binding extent increased from 1 to 4 , whereas in that of the ( R )‐(−)‐enantiomers only between 1 and 4. Structural differences between the serum albumins of three mammalian species possibly cause the enantioselective binding pattern found for the enantiomers of 1–4 , and are responsible for the finding that the binding extent in some cases did not correlate with the lipid solubility of the compounds.