Characterization of two taxol photoaffinity analogues 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 tubulin into microtubules. To characterize the binding site(s) of taxol on the microtubule, taxol-based photoaffinity reagents 1 and 2 bearing photoreactive groups on the A-ring side chain were prepared and evaluated. Taxol analogue 1 exhibits better microtubule assembly activity, greater cytotoxicity toward J774.2 cells, and more specific and efficient photolabeling of the beta-subunit of tubulin than does analogue 2. Therefore, it would appear that 1 is the better candidate for further studies aimed at the characterization of the taxol binding site on the microtubule.
Swindell
C S
CS
Department of Chemistry, Bryn Mawr College, Pennsylvania 19010.
Heerding
J M
JM
Krauss
N E
NE
Horwitz
S B
SB
Rao
S
S
Ringel
I
I
D000345:Affinity Labels / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001386:Azides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D016466:CHO Cells; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D010777:Photochemistry; D043823:Taxoids
D000345:Affinity Labels; D001386:Azides; D043823:Taxoids; C085826:3'-(4-azidobenzamido)taxol; C087207:benzoyltaxol; D017239:Paclitaxel