title: Analysis of drug interactions with very low density lipoprotein by high-performance affinity chromatography.
abstract: 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) × 10(6) M(-1) for R-propranolol and 2.4 (±0.6) × 10(6) 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) × 10(4) M(-1) for R-propranolol and 9.6 (±2.2) × 10(4) 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.
authors.affiliation: Chemistry Department, University of Nebraska, Lincoln, NE, 68588-0304, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Sobansky
authors.forename: David S
authors.initials: DS
authors.lastname: Hage
mesh_terms: D001665:Binding Sites; D002846:Chromatography, Affinity / Q000379:methods*; D007700:Kinetics; D008079:Lipoproteins, VLDL / Q000737:chemistry*; D011433:Propranolol / Q000737:chemistry*; D011485:Protein Binding
chemical_list: D008079:Lipoproteins, VLDL; D011433:Propranolol
references.citation: Anal Biochem. 2008 May 1;376(1):154-6
references.pmid: 18294445
references.citation: Mol Pharmacol. 1980 Mar;17(2):187-91
references.pmid: 7393203
references.citation: J Chromatogr A. 2000 Apr 14;875(1-2):447-53
references.pmid: 10839164
references.citation: Electrophoresis. 2001 Oct;22(16):3401-7
references.pmid: 11669517
references.citation: Eur J Pharm Sci. 2002 Mar;15(2):209-15
references.pmid: 11849918
references.citation: J Sep Sci. 2009 Mar;32(5-6):835-53
references.pmid: 19278006
references.citation: Klin Wochenschr. 1972 Apr 1;50(7):364-9
references.pmid: 4554594
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Feb 25;768(1):3-30
references.pmid: 11939555
references.citation: Anal Chem. 1997 Dec 1;69(23):4790-8
references.pmid: 9406530
references.citation: J Pharm Biomed Anal. 2002 Jan 15;27(3-4):607-14
references.pmid: 11755761
references.citation: Anal Biochem. 1985 Oct;150(1):76-85
references.pmid: 3843705
references.citation: Can Med Assoc J. 1968 Feb 3;98(5):246-51
references.pmid: 4965821
references.citation: J Pharm Pharmacol. 1981 Mar;33(3):179-82
references.pmid: 6116764
references.citation: Anal Bioanal Chem. 2012 Apr;403(2):563-71
references.pmid: 22354572
references.citation: J Chromatogr A. 2007 May 18;1149(2):294-304
references.pmid: 17408678
references.citation: J Pharm Sci. 1998 Apr;87(4):411-24
references.pmid: 9548892
references.citation: Clin Chim Acta. 1985 Oct 15;151(3):193-216
references.pmid: 3902293
references.citation: Drug Metab Pharmacokinet. 2005 Oct;20(5):309-23
references.pmid: 16272748
references.citation: J Med Chem. 2006 Nov 30;49(24):6958-71
references.pmid: 17125249
references.citation: J Lipid Res. 1993 Aug;34(8):1311-21
references.pmid: 8409765
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Jul 1;870(1):22-6
references.pmid: 18554995
references.citation: Rapid Commun Mass Spectrom. 2008 Jul;22(14):2139-52
references.pmid: 18543375
references.citation: N Engl J Med. 1965 Aug 19;273:410-5
references.pmid: 14328103
references.citation: J Pharm Biomed Anal. 1999 Dec;21(5):1037-43
references.pmid: 10703972
references.citation: Acta Pharmacol Sin. 2013 Aug;34(8):998-1006
references.pmid: 23852086
references.citation: Anal Biochem. 2010 Feb 1;397(1):107-14
references.pmid: 19833090
references.citation: Atherosclerosis. 1990 Nov;85(1):1-14
references.pmid: 2149271
references.citation: Anal Chem. 1994 Nov 1;66(21):3814-22
references.pmid: 7802261
references.citation: Anal Biochem. 2005 Nov 15;346(2):300-10
references.pmid: 16225836
references.citation: Curr Med Chem. 2002 Aug;9(15):1463-81
references.pmid: 12173977