Design, Synthesis and Catalytic Activity of Protein Containing Thiotyrosine as an Active Site Residue - Archive ouverte HAL Access content directly
Journal Articles ChemBioChem Year : 2024

Design, Synthesis and Catalytic Activity of Protein Containing Thiotyrosine as an Active Site Residue

Abstract

Native chemical ligation is a key reaction in the toolbox of chemical methods for the synthesis of native and modified proteins. The catalysis of ligation is commonly performed by using small aryl-thiol molecules added at high concentrations. In this work, we incorporated thiotyrosine, a non-canonical amino acid containing an aryl-thiol moiety, into a designed cyclic protein « sans queue ni tête ». Importantly, the protein environment reduced the pKa of the thiol group to 5.8-5.9, which is significantly lower than the previously reported value for thiotyrosine in a short peptide (pKa6.4). Furthermore, we demonstrated the catalytic activity of this protein both as hydrolase and in native chemical ligation of peptides. These results will be useful for the development of efficient protein catalysts (enzymes) for protein synthesis and modification.
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Avant la publication
Thursday, October 3, 2024
Embargoed file
Thursday, October 3, 2024
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Dates and versions

hal-04568169 , version 1 (03-05-2024)

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Thomas Bachelart, Shailesh Kumar, Alexis Jouin, Mo'Ath Yousef, Bruno Kieffer, et al.. Design, Synthesis and Catalytic Activity of Protein Containing Thiotyrosine as an Active Site Residue. ChemBioChem, 2024, ⟨10.1002/cbic.202400148⟩. ⟨hal-04568169⟩
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