Stereoselective Binding of the Enantiomers of Four Closely Related N-Methyl-Barbiturates to Human, Bovine, and Rat Serum Albumin

✍ Scribed by Horst Paul Büch; Regina Krug; Joachim Knabe

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 388 KB
• Volume: 329
• Category: Article
• ISSN: 0365-6233
• DOI: 10.1002/ardp.19963290805

✦ Synopsis

Albumin binding for the enantiomers of fcwr closely related N-methyl-5-phenyl-5-alky I-barbiturates 1 4 was investigated for three different mainmatian species by means of equilibrium dialysis. Lipid solubility (rr-heptanelphosphate buffer distribution coefficientj increased stepwise by a factor of 56 from 1 to 4. Bovine serum albumin: The (S)-(+)-enantiarners of 1-4 were bound in a higher percentage than the (R)-(-)-enatitiomers; lengthening of the aliphatic side-chain increased the hindinp extent in both enantiomeric groups.

Human

serum albumin: Binding of (.S)-(+bI and (S)-(+)-4 wxs higher than that of thc (K)-(-)-cnantiomcrs; with (S)-(+)-2 and (S)-(+)-3 it was much lower than that of the corresponding (R)-(-1-enantiomers. Lengthening of the aliphatic qide chain increased the binding extent of the (S)-(+)as well a h of the (R)-(-)-enantiomers, but with two exceptions: 1. The (.S)-(+)-l binding exceeded that of the (S)-(+)-2 by a factor of nearly two. 9 . The binding extent of (R)-(-)-4 was not further increased in comparison to [R)-(-)-3. Rat serum albumin: (S)-(+)-l and (S)-(+)-2 were hound in a lower percentage than the (K)-(-)-enantionier~, hoth 3-enantiom-CIS showing an equal binding extent; tS)-(+)-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)-(-)-enantioniers 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.