The role of configuration and conformation in the binding of 2,3-benzodiazepines to human serum albumin.
2,3-Benzodiazepines containing a centre of asymmetry at C-5 possess both central and helical chiralities, and the solution of their racemates contains four molecular species. The binding of these compounds to human serum albumin (HSA) was studied by affinity chromatography. The binding strength depended both on the steric orientation of the 5-ethyl substituent and on the conformation of the diazepine ring. Conformation P (defined by the positive sign of C-1-N-2-N-3-C-4 torsion angle) is favoured, while the quasiaxial orientation of the 5-ethyl substituent is not favoured by the albumin molecule.
Visy
J
J
Central Research Institute for Chemistry, Hungarian Academy of Sciences, Budapest.
Simonyi
M
M
D001569:Benzodiazepines / Q000378:metabolism*; D002846:Chromatography, Affinity; D002855:Chromatography, Thin Layer; D006207:Half-Life; D006801:Humans; D008968:Molecular Conformation; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D013237:Stereoisomerism
D012709:Serum Albumin; D001569:Benzodiazepines