PNC-27 is a highly targeted anti-cancer peptide.
It inhibits the binding between the tumor suppressor protein p53 and its negative regulator HDM-2.
HDM-2, an E3 ubiquitin ligase, promotes ubiquitin mediated degradation upon binding to p53.
Cancer cells thus evade the associated growth inhibition and normal apoptosis cycles.
PNC-27 mimics the core segment of the p53 protein (amino acids 12-26) itself, preferentially binding with this HDM-2.
Notably, PNC-27 has a unique segment rich in basic amino acids, aiding in that all too desired penetration of cell membranes.
序列
H-Pro-Pro-Leu-Ser-Gln-Glu-Thr-Phe-Ser-Asp-Leu-Trp-Lys-Leu-Leu-Lys-Lys-Trp-Lys-Met-Arg-Arg-Asn-Gln-Phe-Trp-Val-Lys-Val-Gln-Arg-Gly-OH
化学文摘社编号
1159861-00-3
分子式
C188H293N53O44S
分子量
4031.7990
Research Of PNC-27
1.Mechanism of Action and Membrane Disruption
Releasing this binding allows for full restoration of p53 protein activity; comprehensive regulation of various cancer cell activity at a genetic level follows, suppression of all forms of disease progression being the end result.
The release of p53 then inhibits cancer cell generation, direct apoptosis being one of the end effects.
Subsequent studies focused on the internal mechanism of PNC-27 inhibiting cancer cells within cells.
Research revealed direct disruption of the cancer cell’s plasma membrane – rapid, near irreversible death is induced, with very minimal to no residual effects on normal cells.
Binding to HDM-2 leads PNC-27 (at least partially) to change conformation.
Oligomerization and pore formation is believed to be the final step in this process.
2.Specific Binding
The very specific and high-affinity recognition of HDM-2 by PNC-27 is what makes this peptide so effective.
Release of p53 activity is the primary and central goal of the entire mechanism.
3.Selectively Kills Cancer Cells
PNC specifically binds to abnormally expressed HDM-2 on cancer cells, triggering osmotic imbalance and subsequent membrane dissolution.
This ultimately leads to cell swelling; direct cancer cell death is achieved through an irreversible, rapid mechanism.
Notably, normal cell membranes express only trace amounts of this HDM-2, so healthy cells are not affected.
The physical disruption of the cell membrane itself is what enables this direct killing – pathways relying on p53-mediated intracellular apoptosis signaling are completely separate from this process.
Regardless of the state of the cancer cell’s p53 gene (wild-type, mutated, or otherwise inactivated), as long as detectable HDM-2 expression occurs on the membrane, PNC-27 will effectively eliminate it.
Efficient targeting of cancer cells is possible, even those having developed resistance to both conventional chemotherapy and various forms of radiotherapy; p53 dysfunction is a major cause of such resistance.
A novel therapeutic strategy for treatment-resistant tumors is thus being opened up by this unique mechanism of action.
COA
高效液相色谱法
MS
