Interaction of a new photosensitive derivative of vinblastine, NAPAVIN, with tubulin and microtubules in vitro.
Interaction of a new photosensitive derivative of vinblastine, NAPAVIN, with tubulin and microtubules in vitro.
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长春花碱的新型光敏衍生物 NAPAVIN 与微管蛋白和微管在体外的相互作用。
DOI：
10.1111/j.1432-1033.1990.tb19196.x
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Ponstingl,H
中科院分区：
文献类型：
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作者：
Nasioulas,G;Grammbitter,K;Himes,RH;Ponstingl,H
我们合成了一种新的光反应性长春碱衍生物，3-（{[2-氨基（4-叠氮基-2-硝基苯基）乙基]-氨基}-羰基）-O 4-癸基-3-去（甲氧羰基）-长春碱（NAPAVIN），它可以在455-nm区域的光和紫外线照射下被光活化。先前的研究表明，光活化的NAPAVIN在抑制多药耐药细胞系的细胞增殖方面比长春碱有效得多。本文报道的实验表明，未辐照的衍生物在与脑微管蛋白和微管的相互作用方面与长春碱非常相似，关于抑制体外组装、结合、聚集和产生原丝螺旋。在微管蛋白存在下照射[3 H]NAPAVIN导致药物与蛋白质的两个亚基共价结合。标记也发生时，NAPAVIN第一次照射，然后在黑暗中与微管蛋白孵育，表明一个相当稳定的反应性物种的生产与半衰期约400分钟。我们得出结论，这种化合物的标记，在某些条件下，发生不是由氮烯，但由亲电子光产物。
We have synthesized a new photoreactive vinblastine derivative, 3‐({[2‐amino(4‐azido‐2‐nitrophenyl)ethyl]‐amino}‐carbonyl)‐O4‐decetyl‐3‐de(methoxycarbonyl)‐vincaleukoblastine (NAPAVIN), which can be photo‐activated with light in the 455‐nm region as well as with ultraviolet irradiation. Previous studies had shown that photoactivated NAPAVIN is much more effective than vinblastine in inhibiting cell proliferation of multidrug resistant cell lines. The experiments reported here demonstrate that the unirradiated derivative is very similar to vinblastine in its interactions with brain tubulin and microtubules, regarding inhibition ofin vitroassembly, binding, aggregation, and production of protofilament spirals. Irradiation of [3H]NAPAVIN in the presence of tubulin led to covalent binding of the drug to both subunits of the protein. Labeling also occurred when NAPAVIN was first irradiated, then incubated with tubulin in the dark, indicating the production of a fairly stable reactive species with a half‐life of about 400 min. We conclude that labeling by this compound, under some conditions, occurs not by a nitrene but by an electrophilic photoproduct.