Synthesis and characterization of deoxycholyl 2-deoxyglucuronide: a water-soluble affinity labeling reagent

Acyl glucuronides, which are biosynthesized by the action of glucuronosyltransferases to material for detoxification, are water-soluble and chemically active; they produce irreversible protein adducts via both the transacylation mechanism and the imine mechanism. The acyl group at the C-1 position migrates from the anomeric carbon to the C-2 position of the glucuronic acid moiety, producing the aldehyde group at the C-1 position, where the protein easily condenses through a Schiff's base, in the open-chain aldose form. The elimination of the hydroxyl group at the C-2 position therefore may prevent a protein-bound adduct via the imine mechanism. In this paper, we describe the synthesis and characterization of an acyl 2-deoxyglucuronide of deoxycholic acid as a model compound to investigate its possible utility as a water-soluble affinity labeling reagent for lipophilic carboxylic acids. The solubility of deoxycholyl 2-deoxyglucuronide in an aqueous solution was sufficient under physiological conditions, and the desired material reacted with model peptides to produce covalently bound adducts only via the transacylation mechanism.