Simple and efficient knockdown of His-tagged proteins by ternary molecules consisting of a His-tag ligand,a ubiquitin ligase ligand,and a cell-penetrating peptide |
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Authors: | Takayuki Hattori Koyo Okitsu Norikazu Yamazaki Nobumichi Ohoka Norihito Shibata Takashi Misawa Masaaki Kurihara Yosuke Demizu Mikihiko Naito |
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Institution: | 1. Division of Molecular Target and Gene Therapy Products, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya, Tokyo 158-8501, Japan;2. Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya, Tokyo 158-8501, Japan |
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Abstract: | We designed and synthesized hybrid molecules for a protein knockdown method based on the recognition of a His-tag fused to a protein of interest (POI). The synthesized target protein degradation inducers contained three functional moieties: a His-tag ligand (nickel nitrilotriacetic acid Ni-NTA]), an E3 ligand (bestatin BS] or MV1), and a carrier peptide (Tat or nonaarginine R9]). The designed hybrid molecules, BS-Tat-Ni-NTA, MV1-Tat-Ni-NTA, BS-R9-Ni-NTA, and MV1-R9-Ni-NTA, efficiently degraded His-tagged cellular retinoic acid binding protein 2 via the ubiquitin–proteasome system (UPS). This system will become a useful tool for research into selective protein degradation inducers that act via the UPS. |
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Keywords: | Protein knockdown His-tag-fused protein Ubiquitin-proteasome system Carrier peptide |
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