Patel, KD, De Zoysa, GH, Kanamala, M, Patel, K, Pilkington, LI, Barker, D, Reynisson, J, Wu, Z and Sarojini, V (2019) Novel Cell-Penetrating Peptide Conjugated Proteasome Inhibitors: Anticancer and Antifungal Investigations. Journal of Medicinal Chemistry, 63 (1). pp. 334-348. ISSN 1520-4804

[thumbnail of TAT_Proteasome Inhibitors-JMedChem.docx] Text
TAT_Proteasome Inhibitors-JMedChem.docx - Accepted Version
Available under License Creative Commons Attribution Non-commercial.

Download (3MB)


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.

Item Type: Article
Additional Information: The final accepted version of this article can be found at;
Uncontrolled Keywords: Novel, Cell-penetrating, peptide, proteasome inhibators, anticancer, antifungal, investigations.
Subjects: Q Science > Q Science (General)
Q Science > QH Natural history > QH301 Biology
Q Science > QR Microbiology
Divisions: Faculty of Medicine and Health Sciences > School of Pharmacy and Bioengineering
Related URLs:
Depositing User: Symplectic
Date Deposited: 17 Jan 2020 11:26
Last Modified: 04 Dec 2020 01:30

Actions (login required)

View Item
View Item