The precise regulation of proteasome activity has become a focal point in current research, particularly its implications in cancer treatment. Bortezomib is used for treating multiple myeloma and is found to be ineffective against solid tumors. A spatiotemporal control over the proteasome is one of the solutions to resolve these issues using external stimuli, such as light. Thus, we designed and synthesized azobenzene-containing tripeptide vinyl sulfones 1, 2, 3, and 4, as the azobenzene moiety can impart E↔Z isomerism upon exposure to UV light. Further, the hydrophobicity of these peptides was fine-tuned by systematically varying the size of hydrophobic amino acids at the P1, P2, and P3 positions. The light-induced Z isomers of these photopeptides showed excellent cellular potency in HeLa, MCF-7, and A549 cell lines. Photopeptide 4 with valine at the proximal position, phenylalanine at P2, and leucine at the P1 positions exhibited 19.3- and 6.6-fold cellular potency in MCF-7 and A549 cells, respectively.

中文翻译：

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偶氮苯标签的光肽在 MCF-7 细胞中表现出优异的选择性和光诱导的细胞毒性，优于 HeLa 和 A549


蛋白酶体活性的精确调节已成为当前研究的重点，尤其是其在癌症治疗中的影响。硼替佐米用于治疗多发性骨髓瘤，被发现对实体瘤无效。对蛋白酶体的时空控制是使用外部刺激（例如光）解决这些问题的解决方案之一。因此，我们设计合成了含偶氮苯的三肽乙烯基砜 1、2、3 和 4，因为偶氮苯部分在暴露于紫外光时可以赋予 EZ↔异构。此外，通过系统地改变 P1、P2 和 P3 位点疏水氨基酸的大小，可以微调这些肽的疏水性。这些光肽的光诱导 Z 异构体在 HeLa、MCF-7 和 A549 细胞系中表现出优异的细胞效力。近端位置带有缬氨酸、P2 处苯丙氨酸和 P1 位置亮氨酸的光肽 4 在 MCF-7 和 A549 细胞中分别表现出 19.3 倍和 6.6 倍的细胞效力。