Cellular signal-specific peptide substrate is essential for the gene delivery system responding to cellular signals

Jeong Hun Kang, Riki Toita, Tetsuro Tomiyama, Jun Oishi, Daisuke Asai, Takeshi Mori, Takuro Niidome, Yoshiki Katayama

    Research output: Contribution to journalArticlepeer-review

    4 Citations (Scopus)

    Abstract

    Recently, there is a growing interest in the intracellular signal-targeting gene therapy or diagnosis, mainly by using the reaction of targeting enzymes with peptide substrates. In the present study, we proved the importance of target intracellular signal-specificity peptide substrate for intracellular signals-targeting gene therapy or diagnosis. Protein kinase C (PKC) was used as a trigger to activate the transgene expression. Two peptides, a positive peptide showing phosphorylation levels on several PKC isozymes (PKCα, βII, γ, ε, η, ζ, and ι/λ) and a negative peptide in which the phosphorylation site was destroyed by changing from serine to alanine, were designed. Moreover, two polymers possessing each peptide as a pendant chain, a PKC-responsive conjugate [PPC(S)] and a negative control conjugate [PPC(A)], were synthesized. After the introduction of complexes into cells or tissues, gene expression for PPC(S)/DNA complexes was higher that for PPC(A)/DNA complexes. However, no difference in gene expression between B16 melanoma tumors and normal skin tissues was identified. These results suggest that a peptide substrate specific to a target intracellular signal is very important for intracellular signals-targeting gene therapy or diagnosis.

    Original languageEnglish
    Pages (from-to)6082-6086
    Number of pages5
    JournalBioorganic and Medicinal Chemistry Letters
    Volume19
    Issue number21
    DOIs
    Publication statusPublished - Nov 1 2009

    All Science Journal Classification (ASJC) codes

    • Biochemistry
    • Molecular Medicine
    • Molecular Biology
    • Pharmaceutical Science
    • Drug Discovery
    • Clinical Biochemistry
    • Organic Chemistry

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