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Chemical Synthesis of Native S‐Palmitoylated Membrane Proteins through Removable‐Backbone‐Modification‐Assisted Ser/Thr Ligation
Author(s) -
Huang DongLiang,
Montigny Cédric,
Zheng Yong,
Beswick Veronica,
Li Ying,
Cao XiuXiu,
Barbot Thomas,
Jaxel Christine,
Liang Jun,
Xue Min,
Tian ChangLin,
Jamin Nadège,
Zheng JiShen
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201914836
Subject(s) - native chemical ligation , chemical modification , chemistry , membrane , chemical synthesis , combinatorial chemistry , palm , membrane protein , biochemistry , ligation , biology , in vitro , microbiology and biotechnology , physics , quantum mechanics
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 (RBM GABA ‐assisted STL). This method involves two critical steps: 1) synthesis of S‐palm peptides by a new γ‐aminobutyric acid based RBM (RBM GABA ) 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 RBM GABA ‐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.