Interaction of taxol with human serum albumin

Taxol (paclitaxel) is an anticancer drug, which interacts with microtuble p roteins, in a manner that catalyzes their formation from tubulin and stabil izes the resulting structures (Nogales et al., Nature 375 (1995) 424-427). This study was designed to examine the interaction of taxol with human seru m albumin (HSA) in aqueous solution at physiological pH with drug concentra tions of 0.0001-0.1 mM, and HSA (fatty acid free) concentration of 2% w/v. Cel electrophoresis, absorption spectra and Fourier transform infrared (FTI R) spectroscopy with self-deconvolution and second-derivative resolution en hancement were used to determine the drug binding mode, binding constant an d the protein secondary structure in the presence of taxol in aqueous solut ion. Spectroscopic evidence showed that taxol-protein interaction results i nto two types of drug-HSA complexes with overall binding constant of K = 1. 43 x 10(4) M-1. The molar ratios of complexes were of taxol/HSA 30/1 (30 mM taxol) and 90/1 (90 mM taxol) with the complex ratios of 1.9 and 3.3 drug molecules per HSA molecule, respectively. The taxol binding results in majo r protein secondary structural changes from that of the alpha-helix 55 to 3 5% and beta-sheet 22 to 26%, beta-anti 11 to 15% and turn 11 to 16%, in the taxol-HSA complexes. The observed spectral changes indicate a partial unfo lding of the protein structure, in the presence of taxol in aqueous solutio n. (C) 2000 Published by Elsevier Science B.V. All rights reserved.