Francoise Gueritte-Voegelein

Absence of 7-acetyl taxol binding to unassembled brain tubulin

The effect of taxol on microtubule proteins at 0°C is controversial. In order to determine if taxol is unable to bind to unassembled tubulin, as has been hypothesized, the binding of [3H]acetyl taxol has been studied using equilibrium microdialysis. Ac‐taxol bound to microtubules at 37°C and the binding remained stable when the temperature was lowered to 0°C. Ac‐taxol bound also at 0°C to microtubules stabilized with rhazinilam. In contrast, there was no binding of Ac‐taxol to unassembled tubulin, either free tubulin at 0°C or tubulin, complexed with several microtubule poisons, at 0 and 37°C.

Interaction of 7-acetyltaxol with different tubulin assemblies

Equilibrium microdialysis of [3PH]acetyltaxol against different tubulin assemblies showed that: (i) the binding capacity of tubulin does not depend on the temperature; (ii) two classes of ‘polymers’ exist, with respect to Ac‐taxol binding. Some of them (plaques, complex cylinders induced with some polycations and spirals made with rhazinilam) bound Ac‐taxol, as do normal microtubules. In contrast, spirals formed with vinblastine and griseofulvin, rings made with polycations and complex cylinders induced with spermine do not bind Ac‐taxol as is the case with free tubulin.

Synthesis and Separation of New Dibenz[b,d]azonine Atropisomers

Abstract A synthesis of the dibenz[b,d]azonine atropisomers (14) from 2-phenylbenzoic acid is described. This heterocycle belongs to a new series of biaryl compounds with potential antitubulin activity.

Taxoids: 11,12-dihydro-4-deacetyldocetaxel

Abstract 11,12-dihydro-4-deacetyldocetaxel was prepared from 10-deacetylbaccatin III via its reduced derivative at C11, C12. The title compound is not active on microtubules disassembly.