TY - JOUR
T1 - Analysis of drug interactions with very low density lipoprotein by high-performance affinity chromatography
AU - Sobansky, Matthew R.
AU - Hage, David S.
N1 - Publisher Copyright:
© 2014 Springer-Verlag Berlin Heidelberg.
PY - 2014/10
Y1 - 2014/10
N2 - High-performance affinity chromatography (HPAC) was utilized to examine the binding of very low density lipoprotein (VLDL) with drugs, using R/S-propranolol as a model. These studies indicated that two mechanisms existed for the binding of R- and S-propranolol with VLDL. The first mechanism involved non-saturable partitioning of these drugs with VLDL, which probably occurred with the lipoprotein's non-polar core. This partitioning was described by overall affinity constants of 1.2 (±0.3)∈×∈106 M-1 for R-propranolol and 2.4 (±0.6)∈×∈106 M-1 for S-propranolol at pH 7.4 and 37 °C. The second mechanism occurred through saturable binding by these drugs at fixed sites on VLDL, such as represented by apolipoproteins on the surface of the lipoprotein. The association equilibrium constants for this saturable binding at 37°C were 7.0 (±2.3)∈×∈104 M-1 for R-propranolol and 9.6 (±2.2)∈×∈104 M-1 for S-propranolol. Comparable results were obtained at 20 and 27°C for the propranolol enantiomers. This work provided fundamental information on the processes involved in the binding of R- and S-propranolol to VLDL, while also illustrating how HPAC can be used to evaluate relatively complex interactions between agents such as VLDL and drugs or other solutes.
AB - High-performance affinity chromatography (HPAC) was utilized to examine the binding of very low density lipoprotein (VLDL) with drugs, using R/S-propranolol as a model. These studies indicated that two mechanisms existed for the binding of R- and S-propranolol with VLDL. The first mechanism involved non-saturable partitioning of these drugs with VLDL, which probably occurred with the lipoprotein's non-polar core. This partitioning was described by overall affinity constants of 1.2 (±0.3)∈×∈106 M-1 for R-propranolol and 2.4 (±0.6)∈×∈106 M-1 for S-propranolol at pH 7.4 and 37 °C. The second mechanism occurred through saturable binding by these drugs at fixed sites on VLDL, such as represented by apolipoproteins on the surface of the lipoprotein. The association equilibrium constants for this saturable binding at 37°C were 7.0 (±2.3)∈×∈104 M-1 for R-propranolol and 9.6 (±2.2)∈×∈104 M-1 for S-propranolol. Comparable results were obtained at 20 and 27°C for the propranolol enantiomers. This work provided fundamental information on the processes involved in the binding of R- and S-propranolol to VLDL, while also illustrating how HPAC can be used to evaluate relatively complex interactions between agents such as VLDL and drugs or other solutes.
KW - Drug-protein binding
KW - Frontal analysis
KW - High-performance affinity chromatography
KW - Propranolol
KW - Very low density lipoprotein
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U2 - 10.1007/s00216-014-8081-4
DO - 10.1007/s00216-014-8081-4
M3 - Article
C2 - 25103529
AN - SCOPUS:84920707348
SN - 1618-2642
VL - 406
SP - 6203
EP - 6211
JO - Analytical and Bioanalytical Chemistry
JF - Analytical and Bioanalytical Chemistry
IS - 25
ER -