Binding studies of taxanes to human serum albumin by bioaffinity chromatography and circular dichroism.

The binding to human serum albumin (HSA) of the antitumoural drug paclitaxel and of several structural analogues has been characterized by bioaffinity chromatography and circular dichroism. A ranking of the taxanes was obtained for their affinity to the protein by measuring their retention times on an albumin chromatographic column. This also allowed the calculation of the drug bound percentage. Affinity resulted significantly affected by the nature of the isoserinic side chain, the presence of the 1,14-carbonate moiety and the substituent at C-7, showing that the hydrophobicity of the drug is fundamental in the binding process. The analysis demonstrated that the organic solvent highly alters the interaction mechanism of taxanes to the protein and so the affinity results. Circular dichroism experiments supported this hypothesis. Furthermore, taxanes binding to the serum carrier was characterized by displacement chromatography, by adding into the mobile phase selected competitors, (S)-ibuprofen and valproic acid, that are known to bind to specific binding sites on HSA. These experiments established a non-cooperative binding mechanism.