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.

Sarafraz-Yazdi E, Mumin S, Cheung D, Fridman D, Lin B, Wong L, Rosal R, Rudolph R, Frenkel M, Thadi A, Morano WF, Bowne WB, Pincus MR, Michl J

Biomedicines20 Apr 2022Cited by 8 (Europe PMC)

PMID35625682PMCIDPMC9138867DOI10.3390/biomedicines10050945PepBankPUB-35625682

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Summary

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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

2 results from studies that gave the peptide. No result from this study comes from people.

01LabIn vitro (cells)Mechanism
In cancer cells, PNC‑27 and HDM-2 gold labels occurred in approximately equal ratios in layered rings within membrane pores.
In plain wordsIn cells, PNC‑27 and HDM-2 labels formed approximately equal ratios in layered rings within membrane pores.
Peptide
PNC-27
Outcome
Not applicablePore complex organization
Study
n: not reported in source
cancer cells
Outcome group
Receptor activity and mechanism · Cancer
Studied dose
Dose not stated
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
Show in the study text Report a problemFND-3562568202
02LabIn vitro (cells)Mechanism
In untransformed fibroblasts treated with PNC‑27, no membrane pores formed.
In plain wordsIn cells, PNC‑27-treated normal fibroblasts formed no membrane pores.
Peptide
PNC-27
Outcome
Not applicableMembrane pore formation
Study
n: not reported in source
untransformed fibroblasts
Outcome group
Receptor activity and mechanism · Cancer
Studied dose
Dose not stated
Source sentences
Summary
No pores formed in the control, PNC-27-treated untransformed fibroblasts.
Show in the study text Report a problemFND-3562568203

Studies that did not test the peptide alone1

In this study, PNC-27 was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking PNC-27.

03Computer modelNot a test of PNC-27 aloneIn silicoMechanism
In computational models, PNC‑27 and HDM-2 formed predicted 1:1 complexes with the leader sequence pointing away.
In plain wordsIn lab computer models, the PNC‑27 leader sequence pointed away from the predicted complex with HDM-2.
Peptide
PNC-27
Outcome
Not applicableComplex conformation
Study
n: not reported in source
PNC-27 bound to HDM-2
Outcome group
Receptor activity and mechanism · Cancer
Source sentences
Summary
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.
In this study, PNC-27 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking PNC-27.
Show in the study text Report a problemFND-3562568201

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
21 Oct 2026, 15:58 UTC
Study results updated
Version 1
21 Oct 2026, 12:50 UTC
First added · source update from Europe PMC

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