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.
Mano
Nariyasu
N
Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-ku, Sendai 980-8578, Japan.
Nishijima
Akira
A
Saito
Shuntaro
S
Ikegawa
Shigeo
S
Goto
Junichi
J
D000345:Affinity Labels / Q000138:chemical synthesis* / Q000737:chemistry*; D003840:Deoxycholic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry*; D020719:Glucuronides / Q000138:chemical synthesis* / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D012995:Solubility; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014867:Water / Q000737:chemistry*
C481518:1-O-(24-deoxycholyl)-2-deoxyglucopyranuronic acid; D000345:Affinity Labels; D020719:Glucuronides; D003840:Deoxycholic Acid; D014867:Water