PNC-27, an anticancer peptide, contains a HDM-2 binding domain corresponding to p53 residues 12-26 and a transmembrane penetration domain, and has been found to kill cancer cells but not normal cells by inducing membrane lysis. The 3D structure of the p53 residues of It directly superimposed on the structure of the same residues bound to HDM-2, suggesting that the peptide may target HDM-2 in the cell membrane. The researchers found that HDM-2 is present at significant levels in the cell membrane of multiple cancer cells but not in the cell membrane of some non-transformed cell lines. In colocalization experiments, It bound to cell membrane-bound HDM-2.
The researchers transfected a plasmid expressing full-length HDM-2 with a membrane localization signal into non-transformed MCF-10-2A cells that are insensitive to PNC-27 and found that these cells expressing full-length HDM-2 on their cell surface were responsive to PNC-27. Finally, it is concluded that PNC-27 targets HDM-2 in the cancer cell membrane, enabling it to selectively induce membrane lysis in these cells.
More Introduction:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138867/
