Cs. Swindell et al., CHARACTERIZATION OF 2 TAXOL PHOTOAFFINITY ANALOGS BEARING AZIDE AND BENZOPHENONE-RELATED PHOTOREACTIVE SUBSTITUENTS IN THE A-RING SIDE-CHAIN, Journal of medicinal chemistry, 37(10), 1994, pp. 1446-1449
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.