What Is PNC-27 Peptide?
PNC-27 is a synthetic peptide designed to target and destroy cancer cells. It is a member of the PNC family of probe proteins and is designed to attach to malformed (cancer) cells and die by cell necrosis, but normal and healthy cells remain intact.
The PNC-27 peptide contains the HDM2 binding domain and transmembrane domain corresponding to residue 1226 on p53. It can bind to and kill cancer cells through membrane lysis or cell membrane destruction.
Studies and animal studies have shown that the PNC-27 peptide is highly potent and selective in targeting a variety of specific cancers, including pancreatic cancer, breast cancer, leukemia, melanoma, and other cancer strains.
Synonyms: membrane residency peptide (MRP)
Molecular Formula: C188H293N53O44
Molecular Weight: 4031.7
CAS Number: 1159861-00-3
How Does the PNC-27 Peptide Work?
The PNC protein was first theorized and discovered by Doctors Matthew Pincus and Joseph Michel at SUNY Downstate Medical Center in New York in the year 2000. Aimed initially at fighting HIV, PNC-27 showed excellent ability to bind to cancer cells, leaving healthy cells intact and killing them. The PNC-27 cancer peptide is a non-toxic compound that only causes cancer cell death and does not affect all other healthy cells. It attaches to the membranes of individual cancer cells and can puncture those membranes.
As a result, rapid implosion occurs, leading to immediate cell death due to differences in osmotic pressure inside and outside the tumor cells. PNC-27 achieves this because of its affinity for binding to a protein called HDM2. Cancer cells have HDM2 in their cell membranes.
Immediately after administration of the PNC-27 peptide, it moves to HDM2. It is found in the membrane of cancer cells. Binding to them creates pores or holes in the cell membrane, causing “membrane lysis” or death of the cell membrane. This process, in turn, leads to the destruction of cancer cells.
Clinical Studies of the PNC-27 Peptide
In a paper published by the American Association for Cancer Research, Dr. Ehsan Sarafraz Yazdi et al. revealed in-depth how the PNC-27 cancer peptide exerted its effects, and its novel mechanism of action meant for cancer research in 2010. The authors reported that the mechanism of action for PNC-27 is due to the formation of oligomeric pores in the plasma membrane of tumor cells. Oligomeric pores are not formed in untransformed or non-tumor cells. In addition, they pointed out that MDM2 as a target molecule has been shown to result in PNC-27 selectivity over cancer cells because it mislocalized to the plasma membrane of cancer cells.
PNC-27 Side Effects in Studies
Side effects of PNC-27 have been observed in animal studies. These included skin and nasal infections, lacrimal secretions, teary eyes, dry skin, high blood pressure, headaches, lower back pain, nosebleeds, rectal bleeding, taste changes, and excess protein in the urine.
PNC-27 Clinical Trials
Researchers found in a 2009 study that the three-dimensional structure of the p53 residue of PNC-27 could be directly superimposed on the design of the same residue bound to HDM2. As a result, researchers will be able to use PNC-27 and target HDM2 with the membrane of cancer cells. In particular, cancer cells have significant levels of HDM2 in their membranes, whereas non-transformed or non-cancerous cells do not have substantial levels of HDM2. This process allows the PNC-27 peptide to target cancer cells without selectively damaging the surrounding healthy tissue.
In further experiments, transplantation of HDM2 containing a membrane localization signal into non-transformed cells that are less susceptible to PNC-27 has been found to make these cells more sensitive to PNC-27. As a result, this is further evidence that the PNC-27 peptide was able to selectively attack HDM2 in the membrane of cancer cells, destroying them by membrane lysis while leaving healthy cells intact.
In 2010 studies published in cancer chemotherapy and pharmacology discovered that PNC-27 has a cancer cell destruction effect as a whole peptide and no fragment. The knowledge of the peptide forming membrane bone holes in the cancer cell membrane, where the researcher is set to determine whether some pores (component) or peptide is produced.
During the experiment, researchers showed that a total peptide exerts its effect on the cell membrane of cancer cells. Furthermore, it was observed that other transformed cells or non-trans cell cells recovered around cancer cells. From the experimental results, the researcher says that the PNC-27 cancer peptide targets a specific marker in the film of cancer cells. In addition, this mechanism of action extends the life of PNC-27.