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Enantioselective binding to the human organic cation transporter‐1 (hOCT1) determined using an immobilized hOCT1 liquid chromatographic stationary phase
Author(s) -
Moaddel R.,
Patel S.,
Jozwiak K.,
Yamaguchi R.,
Ho P.C.,
Wainer I.W.
Publication year - 2005
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.20195
Subject(s) - chemistry , atenolol , propranolol , enantiomer , enantioselective synthesis , chromatography , organic cation transport proteins , stereochemistry , transporter , organic chemistry , biochemistry , medicine , blood pressure , radiology , catalysis , gene
A liquid chromatography stationary phase containing immobilized membranes obtained from a cell line that expresses the human organic cation transporter (hOCT1–IAM) has been used to study the binding of the enantiomers of propranolol, atenolol, pseudoephedrine, and α‐methylbenzylamine to the immobilized hOCT1. Frontal displacement chromatography was used to determine the binding affinities ( K d values), and the data demonstrate that there was an enantioselective difference in the K d values of the enantiomers of propranolol, atenolol, and pseudoephedrine, while α‐methylbenzylamine did not significantly bind to the transporter. Competitive inhibition studies with the cell line used to create the chromatographic column demonstrated that, for the enantiomers of propranolol, the ratio of the chromatographically determined K d values [ K d (+)‐( R )‐propranolol / K d (−)‐( S )‐propranolol = 2.98] reflected an enantioselective difference in the functional activity of the two enantiomers [IC 50 (+)‐( R )‐propranolol /IC 50 (−)‐( S )‐propranolol = 2.75]. The chromatographically determined K d values were used to construct an initial pharmacophore which contains a hydrogen bond donating site that appears to be responsible for the observed enantioselectivity. Published 2005 Wiley‐Liss, Inc.† Chirality 17:501–506, 2005.