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Painting argyrins blue: Negishi cross-coupling for synthesis of deep-blue tryptophan analogue β-(1-azulenyl)-l alanine and its incorporation into argyrin C
Bioorganic & Medicinal Chemistry ( IF 3.5 ) Pub Date : 2018-03-26 , DOI: 10.1016/j.bmc.2018.03.037
Erik Stempel , Robert Franz-Xaver Kaml , Nediljko Budisa , Markus Kalesse

The argyrins are a family of non-ribosomal peptides that exhibits different biological activities through only small structural changes. Ideally, a biologically active molecule can be tracked and observed in a variety of biological and clinical settings in a non-invasive manner. As a step towards this goal, we report here a chemical synthesis of unnatural deep blue amino acid β-(1-azulenyl)-l alanine with different fluorescence and photophysical properties, which allows a spectral separation from the native tryptophan signal. This might be especially useful for cell localization studies and visualizing the targeted proteins. In particular, the synthesis of β-(1-azulenyl)-l alanine was achieved through a Negishi coupling which proved to be a powerful tool for the synthesis of unnatural tryptophan analogs. Upon β-(1-azulenyl)-l alanine incorporation into argyrin C, deep blue octapeptide variant was spectrally and structurally characterized.



中文翻译:

将精氨酸涂成蓝色:Negishi交叉偶联,用于合成深蓝色色氨酸类似物β-(1-氮杂烯基)-1丙氨酸并将其掺入精氨酸C中

精氨酸是非核糖体肽家族,其仅通过小的结构变化就显示出不同的生物学活性。理想地,可以以无创方式在各种生物学和临床环境中追踪和观察生物活性分子。作为实现这一目标的一个步骤中,我们在这里报告的非天然深蓝色氨基酸β-(1-薁基)的化学合成-丙氨酸与不同的荧光和光物理性质,这允许从天然色氨酸信号的频谱分离。这对于细胞定位研究和可视化目标蛋白质可能特别有用。特别是,β-(1-薁基)的合成-丙氨酸是通过Negishi偶联获得的,该偶联被证明是合成非天然色氨酸类似物的有力工具。在将β-(1-氮杂烯基)-1-丙氨酸掺入精氨酸C后,对深蓝色八肽变体进行了光谱和结构表征。

更新日期:2018-03-26
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