Please use this identifier to cite or link to this item: https://doi.org/10.1002/chir.20195
Title: Enantioselective binding to the human organic cation transporter-1 (hOCT1) determined using an immobilized hOCT1 liquid chromatographic stationary phase
Authors: Moaddel, R.
Patel, S.
Jozwiak, K.
Yamaguchi, R.
Ho, P.C. 
Wainer, I.W.
Keywords: Affinity chromatography
Drug transporters
Immobilized cellular membranes
Pharmacophore modeling
Issue Date: 2005
Citation: Moaddel, R., Patel, S., Jozwiak, K., Yamaguchi, R., Ho, P.C., Wainer, I.W. (2005). Enantioselective binding to the human organic cation transporter-1 (hOCT1) determined using an immobilized hOCT1 liquid chromatographic stationary phase. Chirality 17 (8) : 501-506. ScholarBank@NUS Repository. https://doi.org/10.1002/chir.20195
Abstract: 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 (Kd values), and the data demonstrate that there was an enantioselective difference in the Kd 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 Kd values [K d (+)-(R)-propranolol/Kd (-)-(S)-propranolol = 2.98] reflected an enantioselective difference in the functional activity of the two enantiomers [IC50 (+)-(R)-propranolol/IC50 (-)-(S)-propranolol = 2.75]. The chromatographically determined Kd values were used to construct an initial pharmacophore which contains a hydrogen bond donating site that appears to be responsible for the observed enantioselectivity.
Source Title: Chirality
URI: http://scholarbank.nus.edu.sg/handle/10635/105919
ISSN: 08990042
DOI: 10.1002/chir.20195
Appears in Collections:Staff Publications

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