pH-dependency of basic ligand binding to alpha 1-acid glycoprotein (orosomucoid).
The binding interactions of a series of basic ligands with alpha 1-acid glycoprotein (AAG) were examined as a function of pH. The binding to AAG increased with increasing pH, and the binding data were satisfactorily fitted to a model that incorporates the effect of pH and discriminates the association constants of neutral (non-protonated) and protonated forms of ligands. It was shown that ligands in the neutral form have a markedly higher affinity for AAG than the protonated forms, resulting in a concomitant decrease in the pKa of bound ligands. The u.v.-visible difference spectra generated upon binding of a representative ligand to AAG also showed that there was a contribution to the binding arising from the deprotonation of the ligand. It is suggested that all tested ligands bind similarly to AAG and that hydrophobic interactions dominate high-affinity binding to AAG.
Urien
S
S
Laboratoire de Pharmacologie, Faculté de Médecine, Université Paris XII, Créteil, France.
Brée
F
F
Testa
B
B
Tillement
J P
JP
D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008024:Ligands; D008433:Mathematics; D008962:Models, Theoretical; D009961:Orosomucoid / Q000378:metabolism*; D011485:Protein Binding; D013053:Spectrophotometry
D008024:Ligands; D009961:Orosomucoid