Potential DNA–protein cross-link products formed by sugar degradation products: identification of N6-[2-(N2-2′-deoxyguanosyl)propionyl]lysine

Abstract

Sugar degradation products are formed during heat treatment of food as well as endogenously in vivo. As reactive carbonyl compounds, they react readily with proteins or DNA to form protein- or DNA-bound advanced glycation end products (glycation reaction or Maillard reaction). In this study, we investigated the formation of potential DNA–protein cross-link products from sugar degradation products. 2′-Deoxyguanosine, l-lysine and different carbohydrates were incubated at 37 °C. The sugar degradation products dihydroxyacetone and d,l-glyceraldehyde lead to the formation of two new cross-link products. The new compounds were isolated by preparative high-performance liquid chromatography and identified by spectral data as the two diastereomers of N6-[2-(N2-2′-deoxyguanosyl)propionyl]lysine. In this structure, the e-amino group of lysine and the exocyclic amine group of 2′-deoxyguanosine are linked via a carboxyethyl group, derived from the carbohydrate component. The binding sites and the binding types were confirmed by synthesis of the analogous products from N2-(1-carboxyethyl)guanosine and N α -acetyllysine methyl ester.