Novel Cell-Penetrating Peptide Conjugated Proteasome Inhibitors: Anticancer and Antifungal Investigations.

Reynisson

Abstract

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.

Citation

Reynisson. (2019). Novel Cell-Penetrating Peptide Conjugated Proteasome Inhibitors: Anticancer and Antifungal Investigations. Journal of Medicinal Chemistry, 334-348. https://doi.org/10.1021/acs.jmedchem.9b01694

• Acceptance Date: Dec 3, 2019
• Publication Date: Dec 4, 2019
• Journal: Journal of Medicinal Chemistry
• Print ISSN: 0022-2623
• Publisher: American Chemical Society
• Pages: 334-348
• DOI: https://doi.org/10.1021/acs.jmedchem.9b01694
• Keywords: Novel, Cell-penetrating, peptide, proteasome inhibators, anticancer, antifungal, investigations.
• Publisher URL: https://pubs.acs.org/doi/10.1021/acs.jmedchem.9b01694