Identification of [6-Hydroxy-2-(hydroxymethyl)-5-oxo-5,6-dihydro-2H-pyran-3-yl]-cysteine (HHPC) as a Cysteine-specific Modification Formed from 3,4-Dideoxyglucosone-3-ene (3,4-DGE)

Glucose degradation products (GDPs) are formed from glucose and other reducing sugars during heat treatment, for example, in heat-sterilized peritoneal dialysis fluids or foods. Because of their reactive mono- and dicarbonyl structure, they react readily with proteins, resulting in the formation of advanced glycation end products (AGEs), loss of protein functionality, and cytotoxicity. Among the GDPs, 3,4-dideoxyglucosone-3-ene (3,4-DGE) exerts the strongest effects despite its relatively low concentration levels. The goal of the present study was therefore to identify the structure of specific protein modifications deriving from 3,4-DGE. A nonapeptide containing the reactive amino acids lysine, arginine, and cysteine was incubated with 3,4-DGE and the dominant GDPs 3-deoxyglucosone (3-DG) and 3-deoxygalactosone (3-DGal) in concentrations as present in peritoneal dialysis fluids (235 μM 3-DG, 100 μM 3-Gal, and 11 μM 3,4-DGE). Glycation rate and product formation were determined by ultra-HPLC–MS/MS (UHPLC–...