Identification and analysis of stereoselective drug interactions with low-density lipoprotein by high-performance affinity chromatography

Matthew R. Sobansky, David S. Hage

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Columns containing immobilized low-density lipoprotein (LDL) were prepared for the analysis of drug interactions with this agent by high-performance affinity chromatography (HPAC). R/S-Propranolol was used as a model drug for this study. The LDL columns gave reproducible binding to propranolol over 60 h of continuous use in the presence of pH 7.4 0.067 M potassium phosphate buffer. Experiments conducted with this type of column through frontal analysis indicated that two types of interactions were occurring between R-propranolol and LDL, while only a single type of interaction was observed between Spropranolol and LDL. The first type of interaction, which was seen for both enantiomers, involved non-saturable binding; this interaction had an overall affinity (nK a) of 1.9 (±0.1)×10 5 M -1 for R-propranolol and 2.7 (±0.2)× 10 5 M -1 for S-propranolol at 37 °C. The second type of interaction was observed only for R-propranolol and involved saturable binding that had an association equilibrium constant (K a) of 5.2 (±2.3)×105 M-1 at 37 °C. Similar differences in binding behavior were found for the two enantiomers at 20 °C and 27 °C. This is the first known example of stereoselective binding of drugs by LDL or other lipoproteins. This work also illustrates the ability of HPAC to be used as a tool for characterizing mixed-mode interactions that involve LDL and related binding agents.

Original languageEnglish (US)
Pages (from-to)563-571
Number of pages9
JournalAnalytical and Bioanalytical Chemistry
Volume403
Issue number2
DOIs
StatePublished - Apr 1 2012

Keywords

  • Drug interactions
  • High-performance affinity chromatography
  • Low-density lipoprotein
  • Propranolol
  • Stereoselective binding

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry

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