Probing the Pore Drug Binding Site of Microtubules with Fluorescent Taxanes: Evidence of Two Binding Poses
Probing the Pore Drug Binding Site of Microtubules with Fluorescent Taxanes: Evidence of Two Binding Poses
复制标题
DOI：
10.1016/j.chembiol.2010.02.006
复制
发表时间：
2010-03-26
影响因子：
--
通讯作者：
Diaz, J. Fernando
中科院分区：
文献类型：
--
作者：
Barasoain, Isabel;Garcia-Carril, Ana M.;Diaz, J. Fernando
微管中的孔位点已经用来自紫杉醇的荧光探针Hexandetax研究。该化合物在细胞中具有活性，与紫杉醇具有相似的作用，表明孔可能是微管稳定剂的靶点。虽然其他紫杉烷以双相方式结合微管，从而指示单一类型的位点，但紫杉醇结合是双相的。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，这可能是由孔中紫杉烷或荧光素部分的不同排列引起的。协会的4-4-20抗荧光素单克隆抗体-己烷紫杉复合物微管保持双相，从而表明，观察到的两个阶段产生的紫杉烷部分的两个不同的姿势。
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.