The effect of colchicine analogues on the reaction of tubulin with iodo[14C]acetamide and N,N′-ethylenebis(iodoacetamide) (original) (raw)

Journal of Biological Chemistry

We have previously found (Ludueiia, R. F., and Roach, M. C. (1981b) Biochemistry 20,[4444][4445][4446][4447][4448][4449][4450] that colchicine and podophyllotoxin inhibit the alkylation of tubulin by iodo["C]acetamide and the formation of an intrachain cross-link in the &tubulin subunit by N,N'-ethylenebis(iodoacetamide) (EBI). It was not clear whether these effects were due to conformational changes in tubulin induced by drugs or to direct steric blockage of the sulfhydryl groups involved. In an effort to characterize further these phenomena, we have examined the effects of single-ring and bicyclic analogues of colchicine on the reaction of tubulin with iodo[14C] acetamide and EBI. We have found that neither the Aring analogues, 3,4,5-trimethoxybenzyl alcohol, 3,4,5-trimethoxybenzaldehyde, 2,3,4-trimethoxybenzaldehyde, and benzaldehyde, nor the C-ring analogues, tropolone and tropolone methyl ether, inhibited alkylation.