Binding properties of human albumin modified by covalent binding of penicillin

Derivatisation of lysine residues in human albumin was performed in vitro b y reaction with penicillin G. This modification reaction has been reported to occur in patients treated with high dosages of the antibiotic. The struc ture of the modified protein was characterised by mass spectrometry and cir cular dichroism. The number of the lysine residues involved depends on the time of incubation and on the drug/protein molar ratio. The secondary struc ture of the modified protein does not change significantly with respect to the native protein. Furthermore, the binding properties of the modified alb umin were characterised by CD spectroscopy. Phenylbutazone, diazepam and bi lirubin, known to bind to specific binding areas, were used as markers. A d ecrease of the affinity to the high-affinity binding sites was observed aft er the modification. (C) 2001 Elsevier Science B.V. All rights reserved.