Effects of synthetic estrogens, (R,R)-(+)-, (S,S)-(-)-, dl- and meso-hexestrol stereoisomers on microtubule assembly.
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.
Sakakibara
Y
Y
Biochemistry Division, Kyoritsu College of Pharmacy, Tokyo, Japan.
Hasegawa
K
K
Oda
T
T
Saitô
H
H
Kodama
M
M
Hirata
A
A
Matsuhashi
M
M
Sato
Y
Y
D000818:Animals; D001921:Brain / Q000648:ultrastructure; D006589:Hexestrol / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008854:Microscopy, Electron; D008868:Microtubule Proteins / Q000378:metabolism*; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure*; D008968:Molecular Conformation; D015394:Molecular Structure; D011108:Polymers; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013552:Swine; D014404:Tubulin / Q000378:metabolism
D008868:Microtubule Proteins; D011108:Polymers; D014404:Tubulin; D006589:Hexestrol