Cell-penetrating peptide conjugated peptide aldehydes Tat-A and Tat-B showed low micromolar anticancer and antifungal activities and synergistic action in combination with cisplatin and amphotericin B against cancer and fungal cells, respectively. Tat-A and Tat-B were significantly more potent than Ixazomib in inhibiting the human 20S proteasomes with IC50 values in the low nanomolar range. Treatment with Tat-A and Tat-B caused membrane disruption and pore formation in HeLa and BE(2)-C cells and inhibition and eradication of C. albicans biofilms. Apoptotic cell death of the treated HeLa and BE(2)-C cells was demonstrated by Annexin V/PI staining. Flow cytometry analyses showed that more than 78% (HeLa) and 92% (BE(2)-C cells showed signs of apoptosis and necrosis upon treatment with Tat-A and Tat-B. This study forms the first report that documents the benefits of cell-penetrating peptide conjugation to enhance the potential of peptide aldehydes as therapeutics.

中文翻译：

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新型细胞穿透肽结合蛋白酶体抑制剂：抗癌和抗真菌研究。

细胞穿透肽缀合的肽醛Tat-A和Tat-B与顺铂和两性霉素B联合使用分别显示出低的微摩尔抗癌和抗真菌活性以及协同作用，分别针对癌细胞和真菌细胞。在抑制人20S蛋白酶体方面，Tat-A和Tat-B的效价比伊沙米单抗显着，IC50值在低纳摩尔范围内。Tat-A和Tat-B处理导致HeLa和BE（2）-C细胞膜破裂和孔形成，并抑制和根除白色念珠菌生物膜。Annexin V / PI染色证明了已处理的HeLa和BE（2）-C细胞凋亡。流式细胞仪分析显示，经过Tat-A和Tat-B处理后，超过78％（HeLa）和92％（BE（2）-C细胞）显示出凋亡和坏死的迹象。