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Thiophene-2,3-Dialdehyde Enables Chemoselective Cyclization on Unprotected Peptides, Proteins, and Phage Displayed
Tongyao Wei1, Dongfang Li1, Yue Zhang1
1Department of Chemistry, State Key Laboratory of Synthetic Organic Chemistry, The University of Hong Kong, Hong Kong, SAR, P. R. China.
Abstract:
Ortho-phthalaldehyde has recently found wide potentials for protein bioconjugation and peptide cyclization. Herein, the second-generation dialdehyde-based peptide cyclization method is reported. The thiophene-2,3-dialdehyde (TDA) reacts specifically with the primary amine (from Lys side chain or peptide N-terminus) and thiol (from Cys side chain) within unprotected peptides to generate a highly stable thieno[2,3-c]pyrrole-bridged cyclic structure, while it does not react with primary amine alone. This reaction is carried out in the aqueous buffer and features tolerance of diverse functionalities, rapid and clean transformation, and operational simplicity. The features allow TDA to be used for protein stapling and phage displayed peptide cyclization.
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