pH dependent binding of ligands to serum lipoproteins.
OBJECTIVE
The binding interactions of binedaline, nicardipine and darodipine with lipoproteins (HDL, LDL, VLDL) were examined as a function of pH in order to evaluate the role of lipoprotein components and ligand protonation in the binding process.


METHODS
Binding studies were performed by equilibrium dialysis with radiolabeled ligands and differential UV-visible spectroscopy.


RESULTS
Deprotonated ligands had a markedly higher affinity for lipoproteins than the protonated forms, resulting in a concomitant decrease in the pKa of bound ligands, i.e., a decrease in the basicity of the ligand in the bound state. The UV-visible difference spectra generated upon binding of auramine O to lipoproteins also showed that there was a contribution to the binding arising from the deprotonation of the ligand. Ligand binding was related to the phospholipid and cholesteryl ester content and to a lesser degree to the free cholesterol and protein content of lipoproteins, therefore to the surface monolayer components of lipoproteins. This relationship was even more accurate for the deprotonated, high-affinity, than for the protonated species.


CONCLUSIONS
It is suggested that among other possible interactions, ligand binding to lipoproteins involves proton exchange between the reactants and that the high affinity ligand species interact more specifically with the phospholipids of the lipoprotein surface monolayer.
Simon
N
N
Laboratoire de Pharmacologie, Faculté de Médecine, Université, Paris XII, France.
Dailly
E
E
Jolliet
P
P
Tillement
J P
JP
Urien
S
S
D006863:Hydrogen-Ion Concentration; D007211:Indoles / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood*; D009529:Nicardipine / Q000097:blood*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000097:blood; D011485:Protein Binding; D013057:Spectrum Analysis
D007211:Indoles; D008074:Lipoproteins; C044680:binedaline; D009529:Nicardipine; D009543:Nifedipine; C034600:darodipine