Cell-penetrating peptide conjugated peptide aldehydes and showed low micromolar anticancer and antifungal activities and synergistic action in combination with cisplatin and amphotericin B against cancer and fungal cells, respectively. and were significantly more potent than Ixazomib in inhibiting the human 20S proteasomes with IC values in the low nanomolar range. Treatment with and caused membrane disruption and pore formation in HeLa and BE(2)-C cells and inhibition and eradication of 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 and . This study forms the first report that documents the benefits of cell-penetrating peptide conjugation to enhance the potential of peptide aldehydes as therapeutics.
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