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.
Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-ku, Sendai 980-8578, Japan.
Nariyasu
N
Mano
Akira
A
Nishijima
Shuntaro
S
Saito
Shigeo
S
Ikegawa
Junichi
J
Goto
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