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J Biol Chem, Vol. 274, Issue 30, 20847-20854, July 23, 1999

Identification of Glutathionyl-3-hydroxykynurenine Glucoside as a Novel Fluorophore Associated with Aging of the Human Lens

Brett Garner^§, Santiago Vazquez^§, Renate Griffith^§, Robyn A. Lindner^§, John A. Carver^§, and Roger J. W. Truscott^§

From the  Australian Cataract Research Foundation and the ^§ Department of Chemistry, University of Wollongong, Wollongong, New South Wales 2522, Australia

A novel fluorophore was isolated from human lenses using high performance liquid chromatography (HPLC). The new fluorophore was well separated from 3-hydroxykynurenine glucoside (3-OHKG) and its deaminated isoform, 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid O-glucoside, which are known UV filter compounds. The new compound exhibited UV absorbance maxima at 260 and 365 nm, was fluorescent (Ex_360 nm/Em_500 nm), and increased in concentration with age. Further analysis of the purified compound by microbore HPLC with in-line electrospray ionization mass spectrometry revealed a molecular mass of 676 Da. This mass corresponds to that of an adduct of GSH with a deaminated form of 3-OHKG. This adduct was synthesized using 3-OHKG and GSH as starting materials. The synthetic glutathionyl-3-hydroxykynurenine glucoside (GSH-3-OHKG) adduct had the same HPLC elution time, thin-layer chromatography R_F value, UV absorbance maxima, fluorescence characteristics, and mass spectrum as the lens-derived fluorophore. Furthermore, the ¹H and ¹³C NMR spectra of the synthetic adduct were entirely consistent with the proposed structure of GSH-3-OHKG. These data indicate that GSH-3-OHKG is present as a novel fluorophore in aged human lenses. The GSH-3-OHKG adduct was found to be less reactive with -glucosidase compared with 3-OHKG, and this could be due to a folded conformation of the adduct that was suggested by molecular modeling.

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