TAXOL-DNA INTERACTIONS - FLUORESCENCE AND CD STUDIES OF DNA GROOVE BINDING-PROPERTIES OF TAXOL

Taxol is perhaps the most successful drug used for the treatment of va rious cancers. Comprehensive literature accumulated on therapeutics of the drug has indicated numerous side effects. In this paper, by use o f fluorescence spectroscopy, it is shown that taxol binds to DNA with an affinity constant (K-a) of 1.08 X 10(7) M-1. This binding is accomp anied by a large 'red edge excitation shift' (REES) of fluorescence em ission maximum in taxol-DNA complex. The results point to an interacti on of taxol with its core eight-membered ring in the DNA groove and th e three phenyl rings projecting away from the DNA. The drug encompasse s about two base pairs of DNA upon binding to it. Systematic studies w ith taxol analogues confirms such a mode of binding. These interesting findings on hitherto unknown taxol-DNA interactions may have clinical implications in view of its large number of side effects and pharmaco kinetics. (C) 1998 Elsevier Science B.V. All rights reserved.