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Chemical Synthesis of Native S-Palmitoylated Membrane Proteins through Removable-Backbone-Modification-Assisted Ser/Thr Ligation.
Angewandte Chemie International Edition ( IF 16.6 ) Pub Date : 2019-12-17 , DOI: 10.1002/anie.201914836
Dong-Liang Huang 1 , Cédric Montigny 2 , Yong Zheng 1 , Veronica Beswick 2, 3 , Ying Li 1 , Xiu-Xiu Cao 1 , Thomas Barbot 2 , Christine Jaxel 2 , Jun Liang 1 , Min Xue 1 , Chang-Lin Tian 1 , Nadège Jamin 2 , Ji-Shen Zheng 1
Affiliation  

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.

中文翻译:

通过可去除的骨干修饰辅助Ser / Thr连接化学合成天然S-棕榈酰化膜蛋白。

天然S-棕榈酰化(S-palm)膜蛋白的制备是化学蛋白合成中尚未解决的挑战之一。在本文中,我们报道了通过可移动骨干修饰辅助的Ser / Thr连接(RBMGABA辅助STL)进行的S-棕榈膜蛋白的首次化学合成。该方法涉及两个关键步骤:1)通过基于新的基于γ-氨基丁酸的RBM(RBMGABA)策略合成S-棕榈肽,以及2)连接S-palm RBM修饰的肽以得到所需的S-棕榈产物通过STL方法。RBMGABA辅助STL方法的实用性通过兔S-手掌肌脂蛋白(SLN)和S-手掌基质2(M2)离子通道的合成得到证明。S-棕榈膜蛋白的合成突显了开发用于化学蛋白合成的非NCL方法的重要性。
更新日期:2020-02-14
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