1. Academic Validation
  2. Anticancer peptide PNC-27 adopts an HDM-2-binding conformation and kills cancer cells by binding to HDM-2 in their membranes

Anticancer peptide PNC-27 adopts an HDM-2-binding conformation and kills cancer cells by binding to HDM-2 in their membranes

  • Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):1918-23. doi: 10.1073/pnas.0909364107.
Ehsan Sarafraz-Yazdi 1 Wilbur B Bowne Victor Adler Kelley A Sookraj Vernon Wu Vadim Shteyler Hunaiz Patel William Oxbury Paul Brandt-Rauf Michael E Zenilman Josef Michl Matthew R Pincus
Affiliations

Affiliation

  • 1 Cell and Molecular Biology Program, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
Abstract

The Anticancer peptide PNC-27, which contains an HDM-2-binding domain corresponding to residues 12-26 of p53 and a transmembrane-penetrating domain, has been found to kill Cancer cells (but not normal cells) by inducing membranolysis. We find that our previously determined 3D structure of the p53 residues of PNC-27 is directly superimposable on the structure for the same residues bound to HDM-2, suggesting that the peptide may target HDM-2 in the membranes of Cancer cells. We now find significant levels of HDM-2 in the membranes of a variety of Cancer cells but not in the membranes of several untransformed cell lines. In colocalization experiments, we find that PNC-27 binds to cell membrane-bound HDM-2. We further transfected a plasmid expressing full-length HDM-2 with a membrane-localization signal into untransformed MCF-10-2A cells not susceptible to PNC-27 and found that these cells expressing full-length HDM-2 on their cell surface became susceptible to PNC-27. We conclude that PNC-27 targets HDM-2 in the membranes of Cancer cells, allowing it to induce membranolysis of these cells selectively.

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