Specific effectors of actin polymerization have found use as dynamic probes of cellular morphology that may be used to gauge cellular response to stimuli and drugs. Of various natural products that target actin, phalloidin is one of the most potent and selective inhibitors of actin depolymerization. Phalloidin and related members of the phallotoxin family are macrocyclic heptapeptides bearing a characteristic and rigidifying transannular tryptathionine bridge. Here we describe a solid-phase synthesis of a new phalloidin analog as a prototype for library development with the potential for on- and off-bead screening. To validate our method, we labelled the phalloidin derivative with a fluorescent dye which stained actin in CHO cells. Furthermore, a bioassay was developed allowing actin polymerization on beads carrying a phalloidin derivative.

中文翻译：

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具有珠上和珠外肌动蛋白结合活性的新型鬼笔环肽类似物的固相合成†

已经发现肌动蛋白聚合的特定效应子用作细胞形态的动态探针，可用于评估细胞对刺激和药物的反应。靶向肌动蛋白的各种天然产物中，鬼笔环肽是肌动蛋白解聚作用最强和选择性最强的抑制剂之一。鬼笔环肽和鬼笔环毒素家族的相关成员是带有特征性和刚性化的跨环类胰蛋氨酸桥的大环七肽。在这里，我们描述了一种新的鬼笔环肽类似物的固相合成，作为图书馆开发的原型，具有进行磁珠和磁珠筛选的潜力。为了验证我们的方法，我们用荧光染料标记了鬼笔环肽衍生物，该染料将CHO细胞中的肌动蛋白染色。此外，开发了一种生物测定法，使肌动蛋白在带有鬼笔环肽衍生物的珠子上聚合。