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. Issue 18 (15th September 2017)

• Record Type: Journal Article
• Authors: Hattori, Takayuki; Okitsu, Koyo; Yamazaki, Norikazu; Ohoka, Nobumichi; Shibata, Norihito; Misawa, Takashi; Kurihara, Masaaki; Demizu, Yosuke; Naito, Mikihiko
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 18(2017)
• Page Start: 4478
• Page End: 4481
• Publication Date: 2017-09-15
• Subjects: Protein knockdown -- His-tag-fused protein -- Ubiquitin-proteasome system -- Carrier peptide; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.08.001
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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 ] orMV1 ), and a carrier peptide (Tat or nonaarginine [R9 ]). The designed hybrid molecules, BS-Tat-Ni-NTA, MV1-Tat-Ni-NTA, BS-R9-Ni-NTA, andMV1-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.