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1.C.110 The Pore-forming PNC-27 Peptide of 32 aas from the p53 Tumor Suppressor Protein (PNC-27) Family

The 32 amino acid PNC-27 peptide (PPLSQETFSDLWKLLKKWKMRRNQFWVKVQRG) inserts into the membranes of tumor cells and selectively kills them, leaving normal cells unaffected.  This peptide is from the Mdm-2 binding domain of the p53 protein which is selectively cytotoxic to cancer cells.  The NMR structure is available (PDB# 1Q2F; 12QI-A).  The p53 cellular tumor antigen, p53-TAD, is 393 aas in humans and of similar sizes in other animals (Sookraj et al. 2010). Anti-cancer tumor cell necrosis of epithelial ovarian cancer cell lines depends on high expression of the HDM-2 protein in their membranes (Thadi et al. 2020). The HDM-2 protein is highly expressed in the membranes of ovarian cancer cell lines and colocalizes with PNC-27. Thus, the association of PNC-27 with preferentially expressed membrane HDM-2 isoforms results in a model for the formation of transmembrane pores and epithelial ovarian cancer tumor cell necrosis (Thadi et al. 2020).

References associated with 1.C.110 family:

Sarafraz-Yazdi, E., S. Mumin, D. Cheung, D. Fridman, B. Lin, L. Wong, R. Rosal, R. Rudolph, M. Frenkel, A. Thadi, W.F. Morano, W.B. Bowne, M.R. Pincus, and J. Michl. (2022). PNC-27, a Chimeric p53-Penetratin Peptide Binds to HDM-2 in a p53 Peptide-like Structure, Induces Selective Membrane-Pore Formation and Leads to Cancer Cell Lysis. Biomedicines 10:. 35625682
Sookraj, K.A., W.B. Bowne, V. Adler, E. Sarafraz-Yazdi, J. Michl, and M.R. Pincus. (2010). The anti-cancer peptide, PNC-27, induces tumor cell lysis as the intact peptide. Cancer Chemother Pharmacol 66: 325-331. 20182728
Thadi, A., E.M. Gleeson, M. Khalili, M.F. Shaikh, E. Goldstein, W.F. Morano, L.M. Daniels, N. Grandhi, H. Glatthorn, S.D. Richard, P.M. Campbell, E. Sarafraz-Yazdi, M.R. Pincus, and W.B. Bowne. (2020). Anti-Cancer Tumor Cell Necrosis of Epithelial Ovarian Cancer Cell Lines Depends on High Expression of HDM-2 Protein in Their Membranes. Ann Clin Lab Sci 50: 611-624. 33067207