caa a22 4500 477127371 CHVBK 20180405111653.0 cr unu---uuuuu 170330e19970401xx s 000 0 eng 10.1023/A:1012120104615 doi (NATIONALLICENCE)springer-10.1023/A:1012120104615 pH Dependent Binding of Ligands to Serum Lipoproteins [Elektronische Daten] [Nicolas Simon, Eric Dailly, Pascale Jolliet, Jean-Paul Tillement, Saïk Urien] Purpose. 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. Plenum Publishing Corporation, 1997 plasma lipoproteins nationallicence protein binding nationallicence pH nationallicence ligand nationallicence drug transport nationallicence Simon Nicolas Laboratoire de Pharmacologie, Faculté de Médecine, Université, Paris XII, France. INSERM, Paris, France aut Dailly Eric Laboratoire de Pharmacologie, Faculté de Médecine, Université, Paris XII, France. INSERM, Paris, France aut Jolliet Pascale Laboratoire de Pharmacologie, Faculté de Médecine, Université, Paris XII, France. INSERM, Paris, France aut Tillement Jean-Paul Laboratoire de Pharmacologie, Faculté de Médecine, Université, Paris XII, France. INSERM, Paris, France aut Urien Saïk Laboratoire de Pharmacologie, Faculté de Médecine, Université, Paris XII, France. INSERM, Paris, France aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/4(1997-04-01), 527-532 0724-8741 14:4<527 1997 14 11095 https://doi.org/10.1023/A:1012120104615 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012120104615 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Simon Nicolas Laboratoire de Pharmacologie, Faculté de Médecine, Université, Paris XII, France. INSERM, Paris, France aut NATIONALLICENCE 700 1- Dailly Eric Laboratoire de Pharmacologie, Faculté de Médecine, Université, Paris XII, France. INSERM, Paris, France aut NATIONALLICENCE 700 1- Jolliet Pascale Laboratoire de Pharmacologie, Faculté de Médecine, Université, Paris XII, France. INSERM, Paris, France aut NATIONALLICENCE 700 1- Tillement Jean-Paul Laboratoire de Pharmacologie, Faculté de Médecine, Université, Paris XII, France. INSERM, Paris, France aut NATIONALLICENCE 700 1- Urien Saïk Laboratoire de Pharmacologie, Faculté de Médecine, Université, Paris XII, France. INSERM, Paris, France aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/4(1997-04-01), 527-532 0724-8741 14:4<527 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer