Synthesis of the amadori compounds of a bioactive tetrapeptide

Abstract

Amadorijevi spojevi (derivati 1-amino-1-deoksi-D-fruktoze) nastaju reakcijom reducirajućih šećera i aminokiselina, proteina i peptida u ranom stadiju Maillardove reakcije. Dokazano je da ovi spojevi nastaju spontano tijekom skladištenja i obrade hrane, te u fiziološkim uvjetima. U svrhu istraživanja strukture, svojstava i bioaktivnosti Amadorijevih spojeva koji mogu nastati neenzimskom glikacijom prohormona čimbenika rasta TGF-β pod fiziološkim uvjetima, kao modelni spojevi sintetizirani su Amadorijevi spojevi: N-(1-deoksi-2,3:4,5-di-O-izopropiliden-β-D-fruktopiranoz-1-il)-L-leucil-L-seril-Nε-(1-deoksi-2,3:4,5-di-O-izopropiliden-β-D-fruktopiranoz-1-il)-L-lizil-L-leucin, N-(1-deoksi-D-fruktoz-1-il)-L-leucil-L-seril-Nε-(1-deoksi-D-fruktoz-1-il)-L-lizil-L-leucin i L-leucil-L-seril-Nε-(1-deoksi-D-fruktoz-1-il)-L-lizil-L-leucin. Svi sintetizirani spojevi karakterizirani su NMR spektroskopijom i spektrometrijom mase.Amadori compounds (1-amino-1-deoxy-D-fructose derivatives) are formed in the reaction between reducing sugars and amino acids, proteins and peptides in the early stage of the Maillard reaction. These compounds play an important role in the changes during cooking and storage of food, as well as of proteins in vivo. We have examined synthetic approaches to N-(1-deoxy-2,3:4,5-di-O-isopropylidene-β-D-fructopyranos-1-yl)-L-leucyl-L-seryl-Nε-(1-deoxy-2,3:4,5-di-O-isopropylidene-β-D-fructopyranos-1-yl)-L-lysyl-L-leucine, N-(1-deoxy-D-fructos-1-yl)-L-leucyl-L-seryl-Nε-(1-deoxy-D-fructos-1-yl)-L-lysyl-L-leucine and L-leucyl-L-seryl-Nε-(1-deoxy-D-fructos-1-yl)-L-lysyl-L-leucine, as model Amadori compounds suitable for studying the structure, behaviour and bioactivity of compounds which may be formed by non-enzymatic glycation of the prohormone of the transforming growth factor β (TGF-β) in vivo. The identities of Amadori compounds were assessed by using NMR spectroscopy and mass spectrometry