pH-dependence of warfarin binding to α1-acid glycoprotein (orosomucoid)
- Urien, S Laboratoire de Pharmacologie, Faculté de Médecine, F-9401 0 Créteil, Université Paris XII, France.
- Brée, F Laboratoire de Pharmacologie, Faculté de Médecine, F-9401 0 Créteil, Université Paris XII, France.
- Testa, B Institut de Ghimie Thérapeutique, Ecole de Pharmacie, Université de Lausanne, CH-1015 Lausanne, Switzerland.
- Tillement, J P Laboratoire de Pharmacologie, Faculté de Médecine, F-9401 0 Créteil, Université Paris XII, France.
Published in:
- Biochemical Journal. - Portland Press Ltd.. - 1993, vol. 289, no. 3, p. 767-770
English
The binding of warfarin to alpha 1-acid glycoprotein (AAG) was found to increase with decreasing pH. The u.v.-visible difference spectra generated upon binding to AAG at pH 5.0 or 7.4 showed warfarin to bind as the anion. Warfarin-binding data were satisfactorily fitted to a model that incorporates the effect of pH and discriminates the association constants of the non-protonated and protonated binding site of the protein. It was shown that AAG-binding site in the protonated form had a markedly higher affinity for warfarin than the non-protonated form, with a pK value of 7.7 +/- 0.1, which is likely to be a histidine residue. Among other possible interactions, it is suggested that ligand binding to AAG involves a reinforced hydrogen bond.
- Language
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- English
- Open access status
- green
- Identifiers
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- DOI 10.1042/bj2890767
- ISSN 0264-6021
- Persistent URL
- https://sonar.ch/global/documents/106883
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