4.8 Article

Total Synthesis and Structural Characterization of Caveolin-1

期刊

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 60, 期 25, 页码 13900-13905

出版社

WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202100826

关键词

bicelles; membrane proteins; palmitoylation; thioester method; total synthesis

资金

  1. JSPS KAKENHI [JP16H04180]

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In this study, the essential protein Caveolin-1 for caveola formation was chemically synthesized and successfully inserted into the lipid bilayer to form a V-shaped structure. The solid-phase method was used to synthesize peptide segments, and O-acyl isopeptide structures were incorporated to improve solubility. After ligation by the thioester method and the introduction of palmitoyl groups, the obtained polypeptide was inserted into bicelles.
Caveolin-1, which is an essential protein for caveola formation, was chemically synthesized. It is composed of 177 amino acid residues, is triply palmitoylated at the C-terminal region, and is inserted into the lipid bilayer to form a V-shaped structure in the middle of the polypeptide chain. The entire sequence was divided into five peptide segments, each of which was synthesized by the solid-phase method. To improve the solubility of the C-terminal region, O-acyl isopeptide structures were incorporated. After ligation by the thioester method and the introduction of the palmitoyl groups, all the protecting groups were removed and the isopeptide structures were converted into the native peptide bond. Finally, the obtained polypeptide was successfully inserted into bicelles, thus showing the success of the synthesis.

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