HSA binding of HIV protease inhibitors: a high-performance affinity chromatography study.
The binding of HIV protease inhibitors, drugs important for anti-HIV chemotherapy, to HSA was examined by high-performance affinity chromatography. Frontal analysis was first used to determine the amount of anchored protein and the binding capacity for selected markers on this column. Zonal elution experiments then ranked the HSA bound fraction of the examined compounds. Information on the binding region was obtained by competitive zonal elution experiments using probe compounds with known sites on HSA. An allosteric competition between HIV protease inhibitors (PIs) and valproate (a probe for the bilirubin site) was detected, consistent with a noncooperative binding mechanism. No significant competition was observed between the examined compounds and salicylate or ibuprofen, probes for sites I and II, respectively. The observations were confirmed by circular dichroism spectroscopy, based on the change in the induced circular dichroism signals of selected markers for the main binding sites of HSA when ritonavir was added as the competitor. These results were in good agreement with previous literature reports and provide more details on how PIs are transported in plasma and how they may compete with other drugs in the body.
Department of Pharmaceutical Sciences, University of Bologna, Bologna, Italy. carlo.bertucci@unibo.it
Carlo
C
Bertucci
Marco
M
Pistolozzi
Guy
G
Felix
U Helena
UH
Danielson
D001665:Binding Sites; D002846:Chromatography, Affinity; D002942:Circular Dichroism; D017320:HIV Protease Inhibitors / Q000378:metabolism*; D006801:Humans; D015394:Molecular Structure; D011485:Protein Binding; D015203:Reproducibility of Results; D012709:Serum Albumin / Q000378:metabolism*; D013997:Time Factors
D017320:HIV Protease Inhibitors; D012709:Serum Albumin