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Journal article
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, v 10(5), 945
20 Apr 2022
PMID: 35625682
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
PNC-27, a 32-residue peptide that contains an HDM-2 binding domain and a cell-penetrating peptide (CPP) leader sequence kills cancer, but not normal, cells by binding to HDM-2 associated with the plasma membrane and induces the formation of pores causing tumor cell lysis and necrosis. Conformational energy calculations on the structure of PNC-27 bound to HDM-2 suggest that 1:1 complexes form between PNC-27 and HDM-2 with the leader sequence pointing away from the complex. Immuno-scanning electron microscopy was carried out with cancer cells treated with PNC-27 and decorated with an anti-PNC-27 antibody coupled to 6 nm gold particles and an anti-HDM-2 antibody linked to 15 nm gold particles. We found multiple 6 nm- and 15 nm-labeled gold particles in approximately 1:1 ratios in layered ring-shaped structures in the pores near the cell surface suggesting that these complexes are important to the pore structure. No pores formed in the control, PNC-27-treated untransformed fibroblasts. Based on the theoretical and immuno-EM studies, we propose that the pores are lined by PNC-27 bound to HDM-2 at the membrane surface with the PNC-27 leader sequence lining the pores or by PNC-27 bound to HDM-2.
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Details
- Title
- 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
- Creators
- Ehsan Sarafraz-Yazdi - SUNY Downstate Health Sciences UniversityStephen Mumin - New York Blood CenterDiana Cheung - SUNY Downstate Health Sciences UniversityDaniel Fridman - SUNY Downstate Health Sciences UniversityBrian Lin - Department of Pathology, SUNY Downstate Medical Center, Brooklyn, NY, United StatesLawrence Wong - SUNY Downstate Health Sciences UniversityRamon Rosal - Columbia UniversityRebecca Rudolph - American Museum of Natural HistoryMatthew Frenkel - American Museum of Natural HistoryAnusha Thadi - Children's Hospital of PhiladelphiaWilliam F. Morano - Department of Surgery, Drexel University College of Medicine, Philadelphia, PA, United StatesWilbur B. Bowne - Department of Surgery, Drexel University College of Medicine, Philadelphia, PA, United StatesMatthew R. Pincus - Veterans Health AdministrationJosef Michl - Columbia University
- Publication Details
- Biomedicines, v 10(5), 945
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Surgery
- Web of Science ID
- WOS:000803407900001
- Scopus ID
- 2-s2.0-85129394662
- Other Identifier
- 991021860723404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Medicine, Research & Experimental
- Pharmacology & Pharmacy