Demonstration of microtubule-like structures formed with (-)-rhazinilam from purified tubulin outside of cells and a simple tubulin-based assay for evaluation of analog activity.
Demonstration of microtubule-like structures formed with (-)-rhazinilam from purified tubulin outside of cells and a simple tubulin-based assay for evaluation of analog activity.
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DOI：
10.1016/j.abb.2009.05.014
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发表时间：
2009-07-15
影响因子：
3.9
通讯作者：
Hamel E
中科院分区：
文献类型：
--
作者：
Edler MC;Yang G;Katherine Jung M;Bai R;Bornmann WG;Hamel E
(−)-拉西兰是在分离过程中从一种天然产品中自发产生的。在培养的细胞中，它引起微管束的形成，就像紫杉醇引起的那样。在微管蛋白的作用下，(−)-拉扎尼兰会形成一种反常的螺旋聚合物。利用谷氨酸和GTP，我们建立了一种螺旋形成的分析方法，并将其应用于17个带有修饰侧链或不同大小D环的新的(±)-rhazinilam类似物。螺旋的形成与抑制人乳腺癌细胞MCF-7的生长有一定的相关性。只有一个侧链类似物的活性与(±)-拉扎尼仑相当。在这些研究中，我们观察到，从反应混合物中去掉GTP会导致(−)-拉扎尼仑诱导的聚合物的形态发生重大变化，观察到的聚合物中有一半是微管状的，另一半是螺旋状的。这种混合聚合物在0℃下缓慢解体，但微管和螺旋的稳定性没有明显差异。
(−)-Rhazinilam was spontaneously generated from a natural product during isolation. In cultured cells, it causes microtubule bundle formation, like those caused by paclitaxel. With tubulin, (−)-rhazinilam causes formation of an aberrant spiral polymer. Using glutamate and GTP, we developed an assay for spiral formation and applied it to 17 new (±)-rhazinilam analogs with either a modified side-chain or a different size D ring. There was reasonable correlation between spiral formation and inhibition of human MCF-7 breast carcinoma cell growth. Only one side chain analog was as active as (±)-rhazinilam. During these studies, we observed that omitting GTP from the reaction mixture caused a major change in the morphology of the (−)-rhazinilam-induced polymer, with half the observed polymer being microtubule-like and half being spirals. This mixed polymer slowly disassembled at 0 °C, but there was no apparent difference in the lability of the microtubules versus the spirals.
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影响因子：
64.8
作者：
SCHIFF, PB;FANT, J;HORWITZ, SB
通讯作者：
HORWITZ, SB
DOI：
10.1093/jnci/83.11.757
发表时间：
1991-06-05
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
MONKS, A;SCUDIERO, D;BOYD, M
通讯作者：
BOYD, M
影响因子：
2.3
作者：
Baudoin, O;Guénard, D;Guéritte, F
通讯作者：
Guéritte, F
DOI：
10.1083/jcb.91.2.479
发表时间：
1981-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Parness J;Horwitz SB
通讯作者：
Horwitz SB
影响因子：
2.7
作者：
David, B;Sevenet, T;Guenard, D
通讯作者：
Guenard, D