Comparative study of interaction mode of diazepines with human serum albumin and alpha 1-acid glycoprotein

• Published in: Journal of pharmaceutical sciences Vol. 81; no. 1; p. 16
• Main Authors: Maruyama, T, Furuie, M A, Hibino, S, Otagiri, M
• Format: Journal Article
• Language: English
• Published: United States 01.01.1992
• Subjects: Anti-Anxiety Agents - metabolism; Bromazepam - metabolism; Clonazepam - metabolism; Diazepam - metabolism; Flunitrazepam - metabolism; Humans; Orosomucoid - metabolism; Oxazepam - metabolism; Protein Binding; Regression Analysis; Serum Albumin - metabolism; Spectrometry, Fluorescence
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600810104

The binding of nine diazepines to human serum albumin (HSA) and to alpha 1-acid glycoprotein (AGP) was investigated by means of fluorescence and circular dichroism (CD) spectroscopies. The binding parameters of diazepam obtained from fluorescence agreed with those obtained from CD measurements. Diazepines have one tight binding site on both HSA and AGP. The binding parameters (nK) of the diazepine: HSA systems are slightly higher than those of diazepine:AGP systems. The relationship between the binding parameters for these two serum proteins and the physicochemical parameters of diazepines was studied by multiple regression analysis to elucidate the binding mode. Moreover, the effects of long-chain fatty acids and cesium chloride on the binding of diazepines to HSA and AGP were also studied. The driving force for the binding of diazepines to both proteins appears to be hydrophobic interaction. In addition, steric effects and electrostatic interactions may also contribute to the binding of diazepines to HSA and AGP, respectively.