Role of B-ring of colchicine in its binding to tubulin.
The chemical specificity of the colchicine-binding site of tubulin is less stringent for the presence of the B-ring than the A- and C-rings of colchicine, Colchicine analogues with modifications in the B-ring bind to tubulin at the same site as colchicine. Analogues with smaller or no substituents in the B-ring bind tubulin remarkably faster than colchicine. Thus, a compound without the B-ring [2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone] binds tubulin even at 4 degrees C and the binding is almost instantaneous at 37 degrees C. Colcemid and 2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone bind reversibly to tubulin, whereas colchicine and desacetamidocolchicine bind almost irreversibly, suggesting that the size of the B-ring moiety of colchicine is not related to the reversibility of binding. We conclude that although the presence of the B-ring of colchicine does not appear to be an essential prerequisite for the drug-tubulin interaction, the B-ring substituents play an important role in determining the binding properties of colchicine to tubulin.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003078:Colchicine / Q000031:analogs & derivatives / Q000378:metabolism*; D003703:Demecolcine / Q000378:metabolism; D006041:Goats; D007700:Kinetics; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014334:Tropolone / Q000031:analogs & derivatives / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism*
D014404:Tubulin; C030369:desacetamidocolchicine; C030370:2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone; D014334:Tropolone; D003078:Colchicine; D003703:Demecolcine