Chemical Synthesis of Native S‐Palmitoylated Membrane Proteins through Removable‐Backbone‐Modification‐Assisted Ser/Thr Ligation

• Published in: Angewandte Chemie 2020-03, Vol.132 (13), p.5216-5222
• Main Authors: Huang, Dong‐Liang, Montigny, Cédric, Zheng, Yong, Beswick, Veronica, Li, Ying, Cao, Xiu‐Xiu, Barbot, Thomas, Jaxel, Christine, Liang, Jun, Xue, Min, Tian, Chang‐Lin, Jamin, Nadège, Zheng, Ji‐Shen
• Format: Article
• Language: English
• Subjects: Backbone; Chemical synthesis; Chemische Proteinsynthese; Chemistry; Ion channels; Membrane proteins; Membranes; Membranproteine; Peptides; Protein biosynthesis; Protein synthesis; Proteins; S-Palmitoylierung; Sarcolipin; Ser/Thr-Ligation
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.201914836

The preparation of native S‐palmitoylated (S‐palm) membrane proteins is one of the unsolved challenges in chemical protein synthesis. Herein, we report the first chemical synthesis of S‐palm membrane proteins by removable‐backbone‐modification‐assisted Ser/Thr ligation (RBMGABA‐assisted STL). This method involves two critical steps: 1) synthesis of S‐palm peptides by a new γ‐aminobutyric acid based RBM (RBMGABA) strategy, and 2) ligation of the S‐palm RBM‐modified peptides to give the desired S‐palm product by the STL method. The utility of the RBMGABA‐assisted STL method was demonstrated by the synthesis of rabbit S‐palm sarcolipin (SLN) and S‐palm matrix‐2 (M2) ion channel. The synthesis of S‐palm membrane proteins highlights the importance of developing non‐NCL methods for chemical protein synthesis. Native Proteine durch nicht‐native Methoden: Eine RBMGABA‐assistierte STL‐Strategie (removable‐backbone‐modification‐assisted serin/threonine ligation) wurde für die chemische Synthese von nativen S‐palmitoylierten Membranproteinen entwickelt, die bisher durch chemische Synthese nicht zugänglich waren. Die erfolgreiche Synthese von S‐palmitoyliertem Sarcolipin und M2 belegt die Bedeutung von Nicht‐NCL‐Methoden für die chemische Proteinsynthese.