title: pH dependent binding of ligands to serum lipoproteins.
abstract: 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.
authors.affiliation: Laboratoire de Pharmacologie, Faculté de Médecine, Université, Paris XII, France.
authors.forename: N
authors.initials: N
authors.lastname: Simon
authors.forename: E
authors.initials: E
authors.lastname: Dailly
authors.forename: P
authors.initials: P
authors.lastname: Jolliet
authors.forename: J P
authors.initials: JP
authors.lastname: Tillement
authors.forename: S
authors.initials: S
authors.lastname: Urien
mesh_terms: 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
chemical_list: D007211:Indoles; D008074:Lipoproteins; C044680:binedaline; D009529:Nicardipine; D009543:Nifedipine; C034600:darodipine