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論文
- タイトル
- タイトル（英）
- A Stable Bioisostere of Ester-Linked Ubiquitin Chains Enables Decoding of Protein Interactors.
- 参照URL
- https://researchmap.jp/tomita-tk/published_papers/51910612
- 著者
- 著者（英）
- Taguchi Y,Tomita T,Nishizawa T,Nakamura D,Saha S,Oyoshi T,Sato K,Mase N,Saeki Y,Narumi T
- 担当区分
- 概要
- 概要（英）
- Protein ubiquitination is a pivotal posttranslational modification that regulates diverse biological processes depending on the type of ubiquitin chain linkage. Recently, ester-linked ubiquitin chains have been identified, yet their inherent hydrolytic instability has posed a significant challenge for biochemical investigations. In this study, a stable and isosteric amide analog of an ester-linked ubiquitin dimer, is chemically synthesized in which serine (Ser) at position 20 of the proximal ubiquitin is replaced with 2,3-diaminopropionic acid (Dap). The desired amide analog is synthesized using a convergent approach involving the sequential chemoselective ligation of three peptide fragments generated through Fmoc-based solid-phase peptide synthesis. Employing this chemically robust ubiquitin probe, a previously unrecognized interaction is uncovered between Ser20-linked ubiquitin chains and spliceosome-associated factors, notably ubiquitin-specific protease 39. These findings highlight the potential of the ester-to-amide bioisosteric strategy to unlock mechanistic insights into atypical ubiquitin modifications. The approach not only circumvents the intrinsic instability of ester-linked ubiquitin chains but also provides a broadly applicable framework for dissecting their biological roles, paving the way for future discoveries in ubiquitin signaling.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Chembiochem : a European journal of chemical biology
- 巻
- 号
- 開始ページ
- 終了ページ
- 出版年月
- 2025年12月17日
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1002/cbic.202500749
- 共同研究・競争的資金等の研究課題