Contribution of ionization and lipophilicity to drug binding to albumin: a preliminary step toward biodistribution prediction.
Understanding the molecular mechanisms governing albumin binding is a major challenge in absorption-distribution-metabolism-excretion prediction. To gain insight into this complex field, an ultracentrifugation method to measure the drug fraction bound to bovine serum albumin [%B(DAB)] is presented. The second part of the study shows the dependence of the experimental binding parameter on ionization and lipophilicity descriptors (pK(a) and log D(oct)(7.4) for a series of 14 structurally diverse drugs. Finally, a docking strategy is used to rationalize the findings; the results confirm the mostly nonspecific nature of the interaction of albumin with neutral ligands.
Ermondi
Giuseppe
G
Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Via P. Giuria 9, I-10125 Torino, Italy.
Lorenti
Miriam
M
Caron
Giulia
G
D002846:Chromatography, Affinity; D006863:Hydrogen-Ion Concentration; D007477:Ions / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D014461:Ultracentrifugation
D007477:Ions; D004364:Pharmaceutical Preparations; D012710:Serum Albumin, Bovine