The protein sulfenic acid chemotype has emerged as an important post-translational modification and plays pivotal roles in regulating protein function under physiological and pathological conditions. As such, general and versatile tags that selectively identify protein sulfenic acids in cells are required. We present the synthesis of highly functionalized probes that contain an aromatic azide to label alkyne modified sulfenic acids, a glycine residue for isotope incorporation and a biotin residue for affinity enrichment. An acid cleavable group between the biotin and tri-handled aromatic core allows for biotin group removal. These syntheses start with monomethyl-5-nitroisophthalic acid, where the nitro group is converted to the azide and one of the carboxylic acids is coupled to a biotin-tagged amine to give a biotin-tagged aromatic azide. Coupling with   glycine allows the addition of isotope labels to quantify relative sulfenic acid formation compared to control conditions. These compounds are currently being evaluated with bacterioferritin comigratory protein (BCP) and alkyl hydroperoxide reductase subunit C (AhpC), which have been oxidized to the respective sulfenic acids and trapped with a dimedone-containing alkyne. Clicking the azido compounds to the alkyne labeled product will yield mass spectrometrically identifiable adducts. These initial results will allow the use of these versatile reagents in other systems of protein labeling.

Synthesis of tri-functionalized aromatic azides for the detection of protein cysteine oxidation

247th National Meeting (2014)

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