Chemical Synthesis of Native S-Palmitoylated Membrane Proteins through Removable-Backbone-Modification-Assisted Ser/Thr Ligation
Angewandte Chemie International Edition 59(13):5178-5184 Mar 2020 

Huang, Dong-Liang; Montigny, Cedric; Zheng, Yong; Beswick, Veronica; Li, Ying; Cao, Xiu-Xiu; Barbot, Thomas; Jaxel, Christine; Liang, Jun; Xue, Min; Tian, Chang-Lin; Jamin, Nadege; Zheng, Ji-Shen


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. 

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