Rhizoxin is an antitumor drug prepared from the fungus Rhizopus chinensis. It is an inhibitor of microtubule assembly and a potent competitive inhibitor of the binding of tubulin of ansamitocin P-3, a maytansine maytansine analogue. Rhizoxin also weakly inhibits vinblastine binding to tubulin. We have previously found that maytansine and vinblastine differ strikingly from each other in many ways, including their effects on tubulin sulfhydryl groups and on tubulin decay. Since the structure of rhizoxin is very different from that of vinblastine and only slightly resembles that of maytansine, we decided to compare its interaction with tubulin with those of the other two drugs, using systems which discriminate between the effects of the latter two drugs. We found that rhizoxin acts like maytansine in that it completely prevents formation of an intrachain cross-link in β-tubulin by N,N′-ethylenebis(iodoacetamide), whereas vinblastine only partially inhibits this. Half-maximal inhibition of formation of this cross-link was observed at 2.5 µm rhizoxin. We found previously that the rate of binding of tubulin to the fluorescent probe bis(8-anilinonaphthalene 1-sulfonate) is a good indicator of tubulin decay and that vinblastine strongly inhibits this, whereas maytansine has no effect. We here report that rhizoxin acts like maytansine in that it has no effect on decay. Thus, despite the fact that its resemblance to maytansine is small, rhizoxin appears to interact with tubulin in very much the same way as does maytansine.

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This report was supported in part by Grants CA 26376 from the NIH and AQ-0726 from the Robert A. Welch Foundation to R. F. L. and in part by a Grant-in-Aid for Cancer Research from the Japanese Ministry of Education, Science and Culture to S. I.

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