Affinity labeling via deamination reactions.

An electrophilic center at saturated carbon generated by the departure of molecular nitrogen shows minimum discrimination between various nucleophiles. The generation of such a center in the active site of a protein is therefore an attractive way of labeling that active site. The chemistry of deamination reactions will be discussed with respect to the practicality of triggering the deamination in the active sites of proteins. Successful applications of this principle using the N-nitrosamide functionality, the alkyl aryl triazene functionality, and the diazo functionality will be described. Reasons why active-site reagents incorporating this type of covert electrophilicity are more specific than those incorporating an overtly electrophilic center (such as -CO-CH2-Halogen) will be advanced. The actual and potential application of deamination precursors to the specific inhibition of physiological activities in living cells will be discussed.