Barasoain Isabel, García-Carril Ana M, Matesanz Ruth, Maccari Giorgio, Trigili Chiara, Mori Mattia, Shi Jing-Zhe, Fang Wei-Shuo, Andreu José M, Botta Maurizio, Díaz J Fernando
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Ramiro de Maeztu 9, 28040 Madrid, Spain.
Chem Biol. 2010 Mar 26;17(3):243-53. doi: 10.1016/j.chembiol.2010.02.006.
The pore site in microtubules has been studied with the use of Hexaflutax, a fluorescent probe derived from paclitaxel. The compound is active in cells with similar effects to paclitaxel, indicating that the pore may be a target to microtubule stabilizing agents. While other taxanes bind microtubules in a monophasic way, thus indicating a single type of sites, Hexaflutax association is biphasic. Analysis of the phases indicates that two different binding sites are detected, reflecting two different modes of binding, which could arise from different arrangements of the taxane or fluorescein moieties in the pore. Association of the 4-4-20 antifluorescein monoclonal antibody-Hexaflutax complex to microtubules remains biphasic, thus indicating that the two phases observed arise from two different poses of the taxane moiety.
已使用六氟他赛（一种源自紫杉醇的荧光探针）对微管中的孔位点进行了研究。该化合物在细胞中具有活性，其作用与紫杉醇相似，这表明该孔可能是微管稳定剂的一个靶点。虽然其他紫杉烷以单相方式结合微管，表明存在单一类型的位点，但六氟他赛的结合是双相的。对各相的分析表明，检测到两个不同的结合位点，反映了两种不同的结合模式，这可能源于紫杉烷或荧光素部分在孔中的不同排列。4-4-20抗荧光素单克隆抗体-六氟他赛复合物与微管的结合仍为双相，因此表明观察到的两个相源于紫杉烷部分的两种不同构象。
