منابع مشابه
Mechanism of microtubule stabilization by taccalonolide AJ
As a major component of the cytoskeleton, microtubules consist of αβ-tubulin heterodimers and have been recognized as attractive targets for cancer chemotherapy. Microtubule-stabilizing agents (MSAs) promote polymerization of tubulin and stabilize the polymer, preventing depolymerization. The molecular mechanisms by which MSAs stabilize microtubules remain elusive. Here we report a 2.05 Å cryst...
متن کاملSynthetic Reactions with Rare Taccalonolides Reveal the Value of C-22,23 Epoxidation for Microtubule Stabilizing Potency
The taccalonolides are microtubule stabilizers isolated from plants of the genus Tacca. Taccalonolide AF is 231 times more potent than the major metabolite taccalonolide A and differs only by the oxidation of the C-22,23 double bond in A to an epoxy group in AF. In the current study, 10 other rare natural taccalonolides were epoxidized and in each case epoxidation improved potency. The epoxidat...
متن کاملTaccalonolides E and A: Plant-derived steroids with microtubule-stabilizing activity.
During the course of a mechanism-based screening program designed to identify new microtubule-disrupting agents from natural products, we identified a crude extract from Tacca chantrieri that initiated Taxol-like microtubule bundling. Bioassay-directed purification of the extract yielded the highly oxygenated steroids taccalonolides E and A. The taccalonolides caused an increased density of cel...
متن کاملTaccalonolide binding to tubulin imparts microtubule stability and potent in vivo activity.
The taccalonolides are highly acetylated steroids that stabilize cellular microtubules and overcome multiple mechanisms of taxane resistance. Recently, two potent taccalonolides, AF and AJ, were identified that bind to tubulin directly and enhance microtubule polymerization. Extensive studies were conducted to characterize these new taccalonolides. AF and AJ caused aberrant mitotic spindles and...
متن کاملTubulin oligomers and microtubule oscillations. Antagonistic role of microtubule stabilizers and destabilizers.
Several types of non-equilibrium phenomena have been observed in microtubule polymerization, including dynamic instability, assembly overshoot and oscillations. They can be interpreted in terms of interactions between tubulin subunits (= alpha, beta heterodimers), microtubules, and a third state, oligomers, which represent intermediates between microtubule disassembly and the regeneration of as...
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ژورنال
عنوان ژورنال: Bioorganic & Medicinal Chemistry
سال: 2014
ISSN: 0968-0896
DOI: 10.1016/j.bmc.2014.01.012