Taxol (paclitaxel) is an anticancer drug that interacts with microtubule proteins in a manner that catalyzes their formation from tubulin and stabilizes the resulting structures. However, in the human lung tumor cell, the concentration of paclitaxel is highest in the nucleus. Therefore, it was of interest to examine the interaction of taxol with DNA and RNA in aqueous solution at physiological pH. Capillary electrophoresis and Fourier transform infrared (FTIR) difference spectroscopic methods were used to characterize the nature of drugDNA and drugRNA interactions and to determine the taxol binding site, the binding constant, the sequence selectivity, the helix stability, and the biopolymer secondary structure in the taxolpolynucleotide complexes in vitro. The FTIR spectroscopic studies were conducted with taxol/polynucleotide (phosphate) ratios of 1/80, 1/40, 1/20, 1/10, 1/4, and 1/2 with a final DNA(P) or RNA(P) concentration of 12.5 mmol/L, and capillary electrophoresis was performed after incubation of taxol with polynucleotides at ratios of 1/200 to 1/12 with a final polynucleotide concentration of 1.25 mmol/L. Taxol was shown to bind to DNA and RNA at GC, AT, or AU bases and the backbone PO2 group. Two types of binding were observed for taxolDNA with K1 = 1.3 × 104 L mol1 and K2 = 3.5 × 103 L mol1, whereas taxolRNA complexes showed one type of binding with K = 1.3 × 104 L mol1. The taxolpolynucleotide complexation is associated with a partial helix stabilization and no major alterations of B-DNA or A-RNA structure. Key words: DNA, RNA, taxol, binding site, binding constant, conformation, helix stability, electrophoresis, FTIR spectroscopy.
There are two major types of skeletal keratan sulphates