title: A new hexapeptide from the leader peptide of rMnSOD enters cells through the oestrogen receptor to deliver therapeutic molecules.
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.
authors.affiliation: Molecular Biology and Viral Oncology, National Cancer Institute "Fondazione Pascale", Naples, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Borrelli
authors.affiliation: Laedhexa Biotechnologies Inc., QB3@953, San Francisco, CA, USA.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Schiattarella
authors.affiliation: Department of Biotechnology, Friedrich-Loeffler-Institut, Neustadt, Germany.
authors.forename: Roberto
authors.initials: R
authors.lastname: Mancini
authors.affiliation: Department of Biology, University of Naples, Federico II, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pica
authors.affiliation: Department of Biology, University of Naples, Federico II, Italy.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Pollio
authors.affiliation: Department of Biology, University of Naples, Federico II, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Ruggiero
authors.affiliation: Molecular Biology and Viral Oncology, National Cancer Institute "Fondazione Pascale", Naples, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Bonelli
authors.affiliation: Institute of Protein Biochemistry, C.N.R., Naples, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: De Luca
authors.affiliation: Molecular Biology and Viral Oncology, National Cancer Institute "Fondazione Pascale", Naples, Italy.
authors.forename: Franca Maria
authors.initials: FM
authors.lastname: Tuccillo
authors.affiliation: Institute of Protein Biochemistry, C.N.R., Naples, Italy.
authors.forename: Clemente
authors.initials: C
authors.lastname: Capasso
authors.affiliation: Department of Statistics, University of Udine, Udine, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Gori
authors.affiliation: INBIOS - Institute of Genetic and Biophysics, C.N.R., Naples, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Sanseverino
authors.affiliation: Department of Chemical Sciences, University of Naples, Federico II, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Carpentieri
authors.affiliation: Department of Chemical Sciences, University of Naples, Federico II, Italy.
authors.forename: Leila
authors.initials: L
authors.lastname: Birolo
authors.affiliation: Department of Chemical Sciences, University of Naples, Federico II, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Pucci
authors.affiliation: Deutsches Krebsforschungszentrum, Infection and Cancer Program, Abt.F010, Heidelberg, Germany.
authors.forename: Jean
authors.initials: J
authors.lastname: Rommelaere
authors.affiliation: Laedhexa Biotechnologies Inc., QB3@953, San Francisco, CA, USA.
authors.forename: Aldo
authors.initials: A
authors.lastname: Mancini
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004721:Endoplasmic Reticulum / Q000378:metabolism; D019793:Fluorescein / Q000737:chemistry / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D021382:Protein Sorting Signals; D011960:Receptors, Estrogen / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D013482:Superoxide Dismutase / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005456:Fluorescent Dyes; D010446:Peptide Fragments; D021382:Protein Sorting Signals; D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D013482:Superoxide Dismutase; D002945:Cisplatin; D019793:Fluorescein