Associate Professor MIZUNO Toshihisa of the Life Science and Applied Chemistry Group has attracted attention for his research paper, "Efficient Inhibition of TGF-β Signaling via Cytosolic Delivery of a Smad2/3-Binding Peptide Using the Cell-Penetrating PG-Surfactant DKDKC12-K5 to Block Smad2/3 Nuclear Translocation," which focuses on peptide drug discovery targeting intracellular signaling molecules. The research summary was featured on the official website of the American Peptide Society, an international professional society in the field of peptide research.

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American Peptide Society website:https://americanpeptidesociety.org/research/blocking-nuclear-entry/

Peptides and proteins with physiological activity, such as hormones and antibodies, are being put into practical use as drugs (first and second generation biopharmaceuticals) that have fewer off-target side effects compared to conventional small-molecule drugs. On the other hand, because these are highly hydrophilic and cannot spontaneously penetrate into cells, their applications have currently been limited mainly to targeting extracellular receptors.

In recent years, this limitation has been overcome, and new drug discovery research targeting intracellular molecules is progressing. To achieve this, it is necessary to combine peptides and proteins that exert activity within cells with "cell membrane permeable carriers" that promote intracellular translocation. However, most of the methods reported so far have only increased the efficiency of intracellular translocation.

In this study, we developed a novel cell membrane-permeable carrier cpPG that not only translocates into cells but also highly selectively localizes to the cytoplasm. We demonstrated that by using cpPG to deliver peptides bound to signaling molecules into cells, the translocation of those molecules to the cell nucleus can be suppressed. Specifically, we have successfully developed peptide inhibitors that target the TGF-β signaling pathway, which is involved in the proliferation and metastasis of cancer cells.

This achievement presents new guidelines for designing peptide drugs based on the control of nuclear translocation of signaling molecules, and has been widely featured on the official website of the American Peptide Society as a noteworthy study in related fields.