Sakakibara Y, Hasegawa K, Oda T, Saitô H, Kodama M, Hirata A, Matsuhashi M, Sato Y
Biochemistry Division, Kyoritsu College of Pharmacy, Tokyo, Japan.
Biochem Pharmacol. 1990 Jan 1;39(1):167-72. doi: 10.1016/0006-2952(90)90661-4.
We previously reported on the inhibition of microtubule polymerization and the formation of ribbon structures by synthetic estrogens [Sato et al., J Biochem 101: 1247-1252, 1987]. The present investigation aimed to analyse these effects in vitro on stereochemical point of view, using hexestrol isomers ((R,R)-(+)-hexestrol, (S,S)-(-)-hexestrol and meso-hexestrol) and dl-hexestrol. Among hexestrols, dl-hexestrol showed the highest activity in ribbon formation from microtubule proteins at 100 microM. On the other hand, meso-hexestrol was distinguished from others by inhibition of microtubule assembly and formation of a large amount of aggregates from purified tubulin in the presence of MgCl2 and DMSO. These results were discussed with physico-chemical properties of hexestrols, e.g. absolute configurations as well as circular dichroism spectra and solid state carbon-13 nuclear magnetic resonance spectra.
我们之前报道过合成雌激素对微管聚合的抑制作用以及带状结构的形成 [佐藤等人，《生物化学杂志》101: 1247 - 1252，1987年]。本研究旨在从立体化学角度在体外分析这些作用，使用己烯雌酚异构体（(R,R)-(+)-己烯雌酚、(S,S)-(-)-己烯雌酚和内消旋己烯雌酚）以及消旋己烯雌酚。在己烯雌酚中，消旋己烯雌酚在100微摩尔浓度下从微管蛋白形成带状结构方面表现出最高活性。另一方面，内消旋己烯雌酚与其他异构体不同，在氯化镁和二甲基亚砜存在的情况下，它能抑制微管组装并从纯化的微管蛋白形成大量聚集体。这些结果结合己烯雌酚的物理化学性质进行了讨论，例如绝对构型以及圆二色光谱和固态碳 - 13核磁共振光谱。
