Díaz J F, Andreu J M, Jiménez-Barbero J
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Ramiro de Maeztu 9, 28040, Madrid, Spain,
Top Curr Chem. 2009;286:121-49. doi: 10.1007/128_2008_12.
Since the discovery of paclitaxel and its peculiar mechanism of cytotoxicity, which has made it and its analogues widely used antitumour drugs, great effort has been made to understand the way they produce their effect in microtubules and to find other products that share this effect without the undesired side effects of low solubility and development of multidrug resistance by tumour cells. This chapter reviews the actual knowledge about the biochemical and structural mechanisms of microtubule stabilization by microtubule stabilizing agents, and illustrates the way paclitaxel and its biomimetics induce microtubule assembly, the thermodynamics of their binding, the way they reach their binding site and the conformation they have when bound.
自从发现紫杉醇及其独特的细胞毒性机制以来,它及其类似物已成为广泛使用的抗肿瘤药物。人们付出了巨大努力来了解它们在微管中产生作用的方式,并寻找其他具有相同作用但没有低溶解度和肿瘤细胞产生多药耐药性等不良副作用的产品。本章回顾了有关微管稳定剂使微管稳定的生化和结构机制的实际知识,并阐述了紫杉醇及其仿生药物诱导微管组装的方式、它们结合的热力学、它们到达结合位点的方式以及结合时的构象。