A Stable Bioisostere of Ester-Linked Ubiquitin Chains Enables Decoding of Protein Interactors.

ABSTRACT: 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 ubiqui

SUBMITTER: Taguchi Y 

PROVIDER: S-EPMC12789890 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature