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Our synthetic strategy for the hydrophobic glycoprotein is summarized. The reverse-polarity protection strategy, in which the side chain carboxy group is protected as a basic picolyl ester, combined with the O-acylisopeptide method proved to be efficient for the preparation of the hydrophobic glycoprotein by ligation methods, and would be applicable for the synthesis of membrane proteins in the future.

Graphical abstract: A strategy for the synthesis of hydrophobic proteins and glycoproteins

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