Tyrosine, covalent bond with peptides

In a 1963 Pedler lecture, Sanger reported that H-DFP makes a covalent bond with tyrosine in the sequence Arg-TjrThrLys from human and rabbit albumin (Sanger, 1963). Mass spectrometry of human albumin treated with soman, chlorpyrifos oxon, FP-biotin, diehlorvos, and DFP confirmed OP modification on Tyr 411 in peptide LVRY TKKVPQVSTPTL (Li et al, 2007, 2008a), where the underline shows Sanger s sequence and the indieates the labeled tyrosine. 

Similar mass spectrometry experiments with pure human and mouse transferrin (Li et al., 2008c), and with human kinesin showed that the OP label was consistently on tyrosine (Table 56.1). Studies with human plasma identified OP labeling on tyrosine in apolipoprotein and alpha-2-glyco-protein. Aggressive treatment of hiunan albumin with FP-biotin and chlorpyrifos oxon led to identification of seven OP-labeled tyrosines (Ding et al, 2008). Finally, we found that synthetic peptides made a covalent bond with DFP, chlorpyrifos oxon, and dichlorvos (Table 56.1). Mass spectrometry conclusively proved that the OP was attached to tyrosine. 

Figure 16.3 Conceptual illustration of two peptides before (left) and after (right) a chemical reaction with formaldehyde. The amino acids are represented as circles. In this particular peptide, a tyrosine (Y) is located within the epitope (shaded circles). An arginine (R) is located elsewhere in the peptide. Formaldehyde results in the formation of a covalent bond between the two residues, due to a Mannich condensation reaction, as shown on the right. The new configuration prevents antibodies from binding to the epitope on the left. 

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