Chemical protein synthesis elucidates key modulation mechanism of the tyrosine-O-sulfation in inducing strengthened inhibitory activity of hirudin

Authors：Yang, Ye; Liang, Mingchan; Wang, Rui^*; He, Chunmao^*

Source：CHINESE CHEMICAL LETTERS, 2023, 34(5): 107806.

DOI：10.1016/j.cclet.2022.107806

• Tyrosine sulfation
• Hirudin
• Chemical protein synthesis
• Post-translational modification
• Native chemical ligation

Tyrosine sulfation is an important post-translational modification that enhances the inhibitory activity of hirudin. Herein, we developed a facile synthetic strategy to afford the sulfated hirudins with up to three modifications and in multi-milligram scales, after a single HPLC purification step. Through these synthetic proteins, a novel type of modulation mechanism exhibited by tyrosine sulfation was proposed, which would help to delineate the structure-function relationships in other sulfated proteins and more importantly, to serve as a basis for the development of related antithrombotic agents.