Description

PNC-27 – Technical Biochemical Mechanism Profile

(p53-HDM-2 Binding Peptide; Mitochondrial Pore-Forming Peptide – Research Use Only)

PNC-27 is a synthetic 32-amino-acid peptide engineered from the MDM2-binding region of p53 (aa 12–26), fused to a membrane-penetrating leader sequence.
In vitro studies demonstrate selective binding of MDM2/HDM2 overexpressed on cancer cell membranes, leading to peptide-mediated pore formation, loss of membrane integrity, and mitochondrial permeability disruption.

✅ 1. Primary Molecular Targets

• HDM2 (Human MDM2 oncoprotein) — overexpressed in many cancer cell membranes

• Membrane-associated MDM2–p53 interaction complexes

• Mitochondrial outer membrane (secondary binding/pore formation)

PNC-27 interacts with membrane-anchored HDM2, not intracellular nuclear HDM2, suggesting an extracellular interaction domain.

✅ 2. Core Mechanistic Pathway

A. HDM2 Binding

The p53-derived region of PNC-27 contains the canonical FSDLWKLL binding motif that docks into the HDM2 hydrophobic cleft.

Molecular consequences observed in vitro:

• Peptide clustering at the plasma membrane

• Conformational disturbance of HDM2-associated lipid domains

B. Pore Formation / Membrane Permeabilization

After binding, oligomerized PNC-27 forms transmembrane pores:

• Loss of ionic gradient

• Cytosolic influx/efflux of ions

• Rapid membrane destabilization

This mechanism is non-apoptotic and caspase-independent in many in-vitro studies.

✅ 3. Mitochondrial Effects

Secondary localization has shown:

• Mitochondrial membrane depolarization

• Release of cytochrome c

• Activation of mitochondrial damage pathways

This can induce classical apoptotic marker expression despite initial caspase-independent membrane disruption.

✅ 4. Enzymes & Signaling Pathways

✅ 5. Representative Gene & Protein Expression Changes

In cell culture work, researchers monitor:

• ↑ p53 stabilization (due to HDM2 blockade)

• ↑ Bax, Bak

• ↑ Caspase-3, Caspase-9

• ↓ Bcl-2 (anti-apoptotic)

• ↑ γ-H2AX (DNA damage marker)

• ↑ Cytochrome c release (mitochondrial stress)

These readouts align with mitochondrial pathway activation.

✅ 6. Selective Action in Research Models

Membrane localization of HDM2 is significantly higher in malignant cells.
PNC-27 binding requires:

• HDM2 presence

• Lipid raft microdomain integrity

• Transmembrane oligomerization capacity

Normal cells expressing low HDM2 show minimal pore formation in vitro.

✅ 7. Second Messengers & Cellular Responses

✅ Mechanistic Summary

• Synthetic p53-MDM2-binding peptide

• Targets membrane-anchored HDM2 in cancer cell membranes

• Forms transmembrane pores, disrupting membrane integrity

• Induces mitochondrial depolarization and apoptotic signaling cascades

• Distinct from traditional receptor-mediated pathways

✅ Research-Only Classification

PNC-27 is supplied solely for controlled in-vitro laboratory studies.
Not approved for human or animal use, ingestion, injection, or therapeutic application.