Development of a New Family of Thiol Specific Photoactivatable Cross-Linking Agents

Article abstract of DOI:10.1021/jo00126a055

A new family of thiol specific photoactivatable cross-linking agents has been developed by the combination of the bromoacetyl function and the diazopyruvamide group.Various bromoacetyl-diazopyruvoyl (bromoacetyl-DAP) derivatives have been synthesized and their reaction chemistry with thiols investigated and photochemistry explored.The trimodular bioprobe 17 design evolved from application of this chemistry.The trifunctionality of 17 is characterized by the presence of (1) a bromoacetyl function that modifies thiol groups through alkylation, (2) a diazopyruvoyl function which upon photolysis undergoes Wolff rearrangement generating a reactive ketene that can acylate nucleophiles, and (3) a phenolic function that acts as a characterization handle through radioiodination labeling via standard techniques.These bifunctional and trifunctional photoprobes typified by N-bromoacetyl-N'-(3-diazopyruvoyl)-m-phenylenediamine (7a) have been used to successfully cross-link a 14 aa peptide(Q) from the α₂-adrenergic receptor to purified G protein.