A new hexapeptide from the leader peptide of rMnSOD enters cells through the oestrogen receptor to deliver therapeutic molecules

Sci Rep. 2016 Jan 4:6:18691. doi: 10.1038/srep18691.

Abstract

A 24-amino acid leader peptide of a new human recombinant manganese superoxide dismutase can enter cells and carry molecules. Here, we demonstrated that six of the 24 amino acids penetrate cells through a particular gate represented by a specific amino acid sequence of the oestrogen receptor (ER). We analysed the internalization of the synthetic hexapeptide and the cytotoxic activity of the hexapeptide conjugated to cisplatin on a cell line panel. In most cell lines, the hexapeptide delivered an amount of cisplatin that was 2 to 8 times greater than that released by cisplatin when the drug was used alone. This increased delivery increases the therapeutic index of cisplatin and reduces side effects caused by a high dosage or long-term treatment times. We may consider this hexapeptide a new molecular carrier to deliver molecules with therapeutic activity into ER(+) cells for diagnostic purposes and clinical or immune therapy.

MeSH terms

  • Amino Acid Sequence
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cisplatin / chemistry
  • Cisplatin / metabolism
  • Cisplatin / pharmacology
  • Drug Carriers / chemistry*
  • Drug Carriers / metabolism
  • Drug Carriers / pharmacology
  • Drug Screening Assays, Antitumor
  • Endoplasmic Reticulum / metabolism
  • Fluorescein / chemistry
  • Fluorescein / metabolism
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / metabolism
  • Humans
  • Inhibitory Concentration 50
  • Peptide Fragments / chemistry*
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology
  • Protein Sorting Signals
  • Receptors, Estrogen / metabolism
  • Recombinant Proteins / chemistry
  • Superoxide Dismutase / chemistry

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Fluorescent Dyes
  • Peptide Fragments
  • Protein Sorting Signals
  • Receptors, Estrogen
  • Recombinant Proteins
  • Superoxide Dismutase
  • Cisplatin
  • Fluorescein