PNC-27 | CAS 1159861-00-3 | p53-HDM2 Inhibitory Anticancer Peptide (Research Use Only) | Knowlux

Product Description

PNC-27, CAS 1159861-00-3, is a synthetic 32-amino-acid chimeric peptide supplied by Knowlux for laboratory research use. It comprises the p53 transactivation domain segment (residues 12-26) fused to a membrane-residency peptide (MRP) leader sequence that confers cell-penetrating capability. The sequence is 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. The molecular formula is C188H293N53O44S and the molecular weight is 4031.73 g/mol. Each lot is released with a lot-specific COA, MSDS and analytical traceability.

Structural and Mechanistic Clarification: PNC-27 is not a conventional receptor agonist or enzyme inhibitor. It is a membrane-active peptide that exploits the elevated cell-surface expression of HDM-2 on cancer cells. The p53-derived segment adopts an HDM-2-binding conformation upon contact with membrane-bound HDM-2, while the MRP leader sequence drives membrane interaction. The result is selective transmembrane pore formation in cancer cells, leading to ionic imbalance, osmotic collapse, and lysis, with no comparable effect on normal cells that lack the HDM-2 surface display. This mechanism is distinct from the intracellular p53-HDM2 antagonism of small-molecule inhibitors such as nutlin-3.

Molecular Weight and Formula Verification: The molecular formula C188H293N53O44S and molecular weight 4031.73 are confirmed across ChemicalBook, MedChemExpress, PeptideDB, Adooq, BOC Sciences, and MyBioSource. A molecular weight of 4031.72 is reported by the Peptide Institute and TheBiotek; this 0.01 g/mol difference is a rounding artifact. One supplier listing reports a molecular weight of approximately 3164 g/mol and a formula of C151H232N40O37 under CAS 1159861-00-3; this is inconsistent with the consensus 32-residue sequence and is treated as a data entry error. Buyers should verify the formula on the lot-specific COA against the consensus assignment.

Product Parameters

Product Details

1. Overview

PNC-27 is a 32-residue synthetic chimeric peptide designed to exploit a cancer-specific surface marker rather than an intracellular target. The N-terminal segment corresponds to the p53 transactivation domain (residues 12-26), the region of p53 that engages the HDM-2 binding pocket. The C-terminal segment is a membrane-residency peptide (MRP) that confers cell-penetrating and membrane-interacting properties. In published preclinical work, PNC-27 binds cell-membrane-bound HDM-2 within 15 minutes at 50 microg/mL and induces cancer cell death within 0-3 hours. The peptide is active against acute myeloid leukemia (AML) cells in vitro and in vivo, and it retains activity against apoptosis-defective cancer cells because its cytotoxic mechanism is membrane-disruptive rather than apoptosis-dependent. The material supplied under this specification is research-grade and is not intended for human administration.

2. Structure-Activity Relationship

The bipartite architecture of PNC-27 is central to its selectivity. The p53(12-26) segment provides HDM-2 recognition; without this segment, the MRP leader alone does not produce cancer-selective lysis. Conversely, the p53 segment alone is not membrane-permeant and does not achieve the same cytotoxic profile. The Trp-rich character of the p53 segment (Trp14, Trp18, Trp23, Trp26) contributes to membrane insertion and pore formation, while the MRP leader sequence facilitates initial membrane engagement. The methionine at position 21 (Met21) is a potential oxidation site; methionine sulfoxide formation can alter the peptide's membrane interaction and should be monitored where activity is the readout. Unlike disulfide-constrained peptides, PNC-27 is linear and contains no cysteine, so disulfide scrambling is not a stability concern; the principal degradation liabilities are Met21 oxidation and aggregation at high concentration.

3. Research Applications

Published preclinical characterizations describe the following research applications:

• HDM-2 surface-binding and membrane-pore formation studies in cancer cell lines

• Acute myeloid leukemia (AML) research models (in vitro cytotoxicity and in vivo anti-leukemia activity)

• p53-HDM2 interaction domain structure-activity studies (p53 residues 12-26 as the minimal binding segment)

• Membrane-active anticancer peptide mechanism research (apoptosis-independent cytotoxicity)

• Cell-penetrating peptide (CPP) and membrane-residency peptide (MRP) delivery studies

• Reference standard development for HPLC and LC-MS analytical methods

These descriptions are derived from published research and are provided for scientific reference only.

Quality Control

Purity specifications for PNC-27 span the 97% to 99.7% range depending on supplier and grade. MyBioSource specifies >97.0% by RP-HPLC. ChemicalBook supplier listings offer 98% to 99% HPLC purity, with the note that 90-99% grades can be customized. MedChemExpress reports a batch purity of 99.73%, and a ChemScene listing reports 99.01% for a 5 mg lot. The peptide is supplied as a sterile-filtered, white lyophilized powder without additives by at least one supplier. The principal quality consideration is the absence of a compendial monograph: specifications are supplier-defined, and lot-specific COA data should be reviewed rather than relying on a catalogue purity figure. Researchers preparing solutions for quantitative assays should also request methionine sulfoxide content data where Met21 oxidation could confound activity results.

Solubility and Handling

Solubility: PNC-27 solubility data across suppliers require careful interpretation because the reported values span different solvent systems and concentrations. InvivoChem's batch-tested data report DMSO solubility of 25 mg/mL (6.20 mM) for the acetate salt. ChemicalBook supplier listings list solubility as H2O/DMSO without specifying a concentration limit, indicating that both water and DMSO are suitable solvents. MyBioSource recommends reconstitution in sterile 18 megaohm-cm water at not less than 100 microg/mL, with further dilution into aqueous solutions, and does not report DMSO as a primary solvent. Fisher Scientific's listing for the MedChemExpress acetate salt corroborates DMSO solubility at 25 mg/mL. For practical stock preparation, DMSO at 25 mg/mL is the most consistently supported numeric value, and water is viable at lower working concentrations (>=100 microg/mL per MyBioSource). Given the peptide's Trp-rich, amphipathic character, aqueous stock solutions at high concentration may be prone to aggregation; DMSO stocks are preferable for concentrated storage, with dilution into aqueous buffer immediately before use. Prepare solutions fresh and aliquot to avoid repeated freeze-thaw cycles.

Handling Precautions: Use powder-handling containment (glove box or fume hood with particulate control). Avoid inhalation of fine powder. Wear nitrile gloves, lab coat, and eye protection. The Met21 residue is susceptible to oxidation; handle under inert atmosphere where practical and avoid prolonged exposure to air and light. Brief centrifugation before opening is recommended to dislodge lyophilized material from the cap or vial seal.

Storage and Stability

Storage guidance for PNC-27 diverges in a way that reflects the distinction between routine laboratory handling and archival preservation. The lyophilized powder is stable at room temperature for 3 weeks but should be stored desiccated below -18C for long-term preservation. Reconstituted solutions are stable at 4C for 2-7 days, with long-term storage below -18C. The convergence point is that the lyophilized powder should be protected from moisture and light, and that -18C or below is the conservative long-term condition. For reconstituted solutions, the 4C window is short, and frozen aliquots are preferable for extended use. Freeze-thaw cycles should be avoided. The lyophilized powder is hygroscopic; equilibrate vials to room temperature before opening.

Documentation Support

Per lot: COA, MSDS, HPLC chromatogram, and mass spectrometry data. Where available from the supplier, amino acid analysis and methionine sulfoxide content data are provided. Custom specifications and third-party inspection can be arranged on a project basis.

About Knowlux

Knowlux Biotechnology is a GMP-oriented manufacturer and supplier of peptides, APIs and fine-chemical research compounds, operating from Hubei, China. We serve research groups, CDMOs and distributors in more than 40 countries, and support contract synthesis, custom packaging and technical documentation requests.

Compliance Statement

FOR RESEARCH USE ONLY. NOT FOR HUMAN USE. NOT FOR DIAGNOSTIC OR THERAPEUTIC USE.

This product is supplied for laboratory research use only. It is not for human or animal administration, not for diagnostic or therapeutic use, not for retail sale, and not for personal use. PNC-27 is not approved as a medicinal product in any jurisdiction. The purchaser is responsible for verifying product specifications against their specific research requirements and for compliance with all applicable institutional, local, and national regulations governing research chemical acquisition, storage, and use. Research context statements are for scientific reference only and do not constitute medical advice, promotional claims, or dosing guidance.

Data Verification Notes: The molecular formula C188H293N53O44S and molecular weight 4031.73 are confirmed across ChemicalBook, MedChemExpress, PeptideDB, Adooq, BOC Sciences, and MyBioSource. The sequence PPLSQETFSDLWKLLKKWKMRRNQFWVKVQRG is confirmed by ChemicalBook, Adooq, PeptideDB, and the JBC primary literature table. The p53(12-26) and MRP bipartite architecture is described in ChemicalBook and MedChemExpress. The activity data (binding to membrane HDM-2 at 15 min/50 microg/mL; cancer cell death at 0-3 h/50 microg/mL; in vivo AML activity at 40 mg/kg i.p.) are from PeptideDB-curated references. The supplier entry with MW approximately 3164 and formula C151H232N40O37 is noted as a data inconsistency and not adopted. Solubility values are reported with their source conditions rather than reconciled into a single figure. Storage guidance divergence is reported as-is, with the -18C powder condition presented as the conservative archival option.

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