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Stereoselectivity and enantiomer‐enantiomer interactions in the binding of ibuprofen to human serum albumin
Author(s) -
Itoh Tomoo,
Saura Yoshikazu,
Tsuda Yasuyuki,
Yamada Hideo
Publication year - 1997
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/(sici)1520-636x(1997)9:7<643::aid-chir1>3.0.co;2-8
Subject(s) - enantiomer , chemistry , binding site , stereoselectivity , human serum albumin , stereochemistry , binding constant , chirality (physics) , chromatography , biochemistry , catalysis , nambu–jona lasinio model , chiral symmetry breaking , physics , quantum mechanics , quark
Binding of ibuprofen (IB) enantiomers to human serum albumin (HSA) was studied using a chiral fluorescent derivatizing reagent, which enabled the measurement of IB enantiomers at a concentration as low as 5 × 10 −8 M. Scatchard analyses revealed that there were two classes of binding sites for both enantiomers. For the high affinity site, the number of the binding sites was one for both enantiomers, and the binding constant of R‐IB was 2.3‐fold greater than that of S‐IB. The difference in the affinity at the high affinity site may result in the stereoselective binding of IB enantiomers at therapeutic concentrations. It was confirmed that the high affinity site of IB enantiomers is Site II (diazepam binding site) by using site marker ligands. Also, significant enantiomer‐enantiomer interactions were observed in the binding. The binding data were quantitatively analyzed and a binding model with an assumption of competitive interactions only at the high affinity site simulated the binding characteristics of IB enantiomers fairly well. Chirality 9:643–649, 1997. © 1997 Wiley‐Liss, Inc.