Semi-synthesis of disulfide-linked branched tri-ubiquitin mimics

• 来源期刊: 中国科学:化学（英文版）
• 年，卷（期）: 2018,（4）
• 页码范围: 412-417
• 页数: 6页
• 语种: 英文

摘要

Ubiquitin (Ub) chain isopeptide bond mimics are useful molecules for biochemical and biophysical studies.Herein,we report the semi-synthesis of the disulfide-linked K11/K48-branched tri-Ub (Ub311/48(S-S)),the first example of an isopeptide mimic for the branched Ub chains,which have recently emerged as an interesting category of Ub modifications.Our strategy comprised the E1-dependent synthesis of the Ub conjugate of aminoethanethiol,followed by disulfide formation with Ub(K11C,K48C).The structure of the synthetic isopeptide bond mimics was verified by the crystal structure ofUb311/48(S-S).Deubiquitination and pulldown assays indicated that the synthetic Ub311/48(S-S) could be hydrolyzed by linkage-specific deubiquitinases (K11-specific Cezanne and K48-specific OTUB1),and recognized by proteasomal ubiquitin receptor S5a.