Tetrazine-containing amino acid for peptide modification and live cell labeling

Abstract

A novel amino acid derivative 3-(4-(1, 2, 4, 5-tetrazine-3-yl) phenyl)-2-aminopropanoic acid was synthesized in this study. The compound possessed better water-solubility and was synthesizedmore easily compared with the well-known and commercially available 3-(p-benzylamino)- 1, 2, 4, 5-tetrazine. Tetrazine-containing amino acid showed excellent stability in biologicalmedia andmight be used for cancer cell labeling. Moreover, the compound remained relatively stable in 50% TFA/DCM with little decomposition after prolonged exposure at room temperature. The compound could be utilized as phenylalanine or tyrosine analogue in peptide modification, and the tetrazine-containing peptide demonstrated more significant biological activity than that of the parent peptide. The combination of tetrazine group and amino acid offered broad development prospects of the bioorthogonal labeling and peptide synthesis. � 2015 Ni et al.