Stereoselective binding of the enantiomers of warfarin and trytophan to serum albumin from some different species studied by affinity chromatography on columns of immobilized serum albumin

Lagercrantz, Carl; Larsson, Thomas; Denfors, Ingrid

doi:10.1016/0306-4492(81)90153-2

Cited by 41 publications

(45 citation statements)

References 6 publications

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“…354 Besides its involvement in protein synthesis, plasma tryptophan influences the turnover of serotonin (XLIII) in the central nervous Benzodiazepines bind strongly to HSAm and displace tryptophan from its binding Benzodiazepines and bilirubin, however, bind independently of each othe?360 in accordance with the lack of influence of benzodiazepines on the potency of coumarin type anticoag~lants.~~~ The discovery by Muller and Wollert of the high stereospecificity associated with the binding of oxazepam hemisuccinate (LXV) to HSA361 indicated that the benzodiazepine (or indol) binding site possesses high specificity.…”

Section: Stereoselective Binding Of Drugs To Serum Albuminmentioning

confidence: 97%

On chiral drug action

Simonyi

1984

Medicinal Research Reviews

125

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Section: Stereoselective Binding Of Drugs To Serum Albuminmentioning

confidence: 97%

On chiral drug action

Simonyi

1984

Medicinal Research Reviews

125

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“…As an example, literature values for the association equilibrium constants between HSA and R-warfarin in pH 7.4, 0.067 M phosphate buffer have ranged from (2.1 to 3.3) × 10 5 M −1 at 37 • C [10,20,[33][34][35][36]. Part of the variation in these numbers may be due to differences in the experimental errors of the various techniques used in these studies (i.e., zonal elution [10,20,33], equilibrium dialysis [35,36], and frontal analysis [34]). However, the results of this report suggest that part of this variation could also be a result of differences in the way the warfarin solutions were used and stored in these studies.…”

Section: Effects Of Warfarin Stability On Protein Bindingmentioning

confidence: 99%

Stability of warfarin solutions for drug–protein binding measurements: Spectroscopic and chromatographic studies

Moser

Kingsbury

Hage

2006

Journal of Pharmaceutical and Biomedical Analysis

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Warfarin is commonly used in drug-protein binding studies as a displacement marker for Sudlow site I on the protein human serum albumin (HSA). This study examined the stability of aqueous warfarin solutions prepared for such experiments. This was investigated using NMR spectroscopy and affinity chromatography. It was found by 1H NMR that warfarin underwent a slow first-order conversion in aqueous solution. The rate of this reaction increased with temperature, giving rate constants at pH 7.4 of 0.0086 h(-1) at 25 degrees C and 0.041 h(-1) at 37 degrees C. It was concluded from further 1H and 13C NMR studies, along with molecular modeling, that this process involved the conversion of the minor cyclic hemiketal form of warfarin to its major cyclic hemiketal. This reaction had a small but measurable effect on the binding of R- and S-warfarin to HSA, as demonstrated by HPLC using an immobilized HSA affinity column. From this work, general guidelines were developed concerning the usable lifetimes for warfarin that is prepared in aqueous solutions for studies of drug-protein binding.

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“…This result is similar to previous values of 2.4-4.1 × 10 5 M -1 that have been reported for this interaction in the absence of any solubilizing agent. 40,45,46 By using the reciprocal of the slope, the binding capacity of the immobilized HSA column for warfarin could also be obtained from Figure 4(a). This gave an effective concentration of 33 (± 1) μM for the warfarin binding sites in the column.…”

Section: Self-competition Studies With Warfarinmentioning

confidence: 99%

Quantitative Studies of Allosteric Effects by Biointeraction Chromatography: Analysis of Protein Binding for Low-Solubility Drugs

Chen

Hage

2006

Anal. Chem.

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A new chromatographic method was developed for characterizing allosteric interactions between an immobilized binding agent and low solubility compounds. This approach was illustrated by using it to characterize the interactions between tamoxifen and warfarin during their binding to the protein human serum albumin (HSA), with β-cyclodextrin being employed as a solubilizing agent for these drugs. It was confirmed in this work through several experiments that warfarin had a single binding site on HSA with an association equilibrium constant of 2-5 × 10 5 M -1 (average, 3.9 × 10 5 M -1 ) at 37°C, in agreement with previous reports. It was also found that tamoxifen had a single major binding site on HSA, with an association equilibrium constant of 3-4 × 10 7 M -1 (average, 3.5 × 10 7 M -1 ) at 37°C. When warfarin was used as a mobile phase additive in competition studies with tamoxifen, this had a positive allosteric effect on tamoxifen/HSA binding, giving a coupling constant of 2.3 (± 0.3). Competitive studies using tamoxifen as a mobile phase additive indicated that tamoxifen had a negative allosteric effect on warfarin/HSA binding, providing a coupling constant of 0.79 (± 0.03). A unique feature of the technique described in this report was its ability to independently examine both directions of the warfarin/tamoxifen allosteric interaction. This approach is not limited to warfarin, tamoxifen and HSA but can also be used to study other solutes and binding agents.

show abstract

Stereoselective binding of the enantiomers of warfarin and trytophan to serum albumin from some different species studied by affinity chromatography on columns of immobilized serum albumin

Cited by 41 publications

References 6 publications

On chiral drug action

On chiral drug action

Stability of warfarin solutions for drug–protein binding measurements: Spectroscopic and chromatographic studies

Quantitative Studies of Allosteric Effects by Biointeraction Chromatography: Analysis of Protein Binding for Low-Solubility Drugs

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