CHARACTERIZATION OF 2 TAXOL PHOTOAFFINITY ANALOGS BEARING AZIDE AND BENZOPHENONE-RELATED PHOTOREACTIVE SUBSTITUENTS IN THE A-RING SIDE-CHAIN

Taxol is a structurally novel and clinically effective antitumor drug, which, unlike other antimitotic agents, induces the assembly of tubul in into microtubules. To characterize the binding site(s) of taxol on the microtubule, taxol-based photoaffinity reagents 1 and 2 bearing ph otoreactive groups on the A-ring side chain were prepared and evaluate d. Taxol analogue 1 exhibits better microtubule assembly activity, gre ater cytotoxicity toward J774.2 cells, and more specific and efficient photolabeling of the beta-subunit of tubulin than does analogue 2. Th erefore, it would appear that 1 is the better candidate for further st udies aimed at the characterization of the taxol binding site on the m icrotubule.