Untitled

Abstract

Carbohydrate-peptide esters which mimic the reactivity of sugar 6-phosphates in nonenzymatic glycations were used as model compounds for the study of the Maillard reaction in vitro. We found that intramolecular cyclization of the monosaccharide ester in which the sugar moiety (D-glucose or D-galactose) is linked, through the C-6 hydroxy group, to the C-terminal carboxy group of the endogenous opioid pentapeptide leucine-enkephalin, in methanol as the solvent, resulted in the formation of imidazolidinone diastereoisomers having cis or trans relative geometry of the substituents at the imidazolidinone ring moiety. The diastereoisomeric imidazolidinones were separated and each transformed by hydrolysis into the corresponding D-gluco- and D-galacto-related imidazolidinone products of leucine-enkephalin. Along with the previous evidence that, from the same sugar-peptide esters by changing the reaction conditions Amadori rearrangement products could be obtained [Horvat et al. (1998) J Chem Soc Perkin Trans 1:909-13], the presented results point to the possibility that similar carbohydrate-related imidazolidinones may also be generated in the early stage of the Maillard reaction in vivo.

Study of degradation pathways of Amadori compounds obtained by glycation of opioid pentapeptide and related smaller fragments: Stability, reactions, and spectroscopic properties

“…As reported earlier, [21][22][23]26 the equilibrium compositions of the Amadori compounds 1-4 show in water and DMSO solution pyranose and furanose forms, the ␤-pyranose tautomer being the most abundant. Quite surprisingly, DMSO solutions of compounds 1-4 contain at equilibrium a relatively high proportion of the acyclic hydrate form (ca.…”

“…[21][22][23] We found that glycation of leucine-enkephalin at the Nterminal induces changes in the peptide conformation and results in total loss of opioid activity in vitro. 24 These findings are not only of theoretical interest since similar adducts with altered interactions with endogenous opioid receptors can be formed during exposure of enkephalins, or other opioid peptides, to glucose in vivo.…”

Stereochemical Assignment of Diastereomeric Imidazolidinone‐Ring‐Containing Bicyclic Sugar‐Peptide Adducts: NMR Spectroscopy and Molecular Calculations

“…[26] NMR Spectroscopy: NMR experiments were carried out at a concentration of 6 m in CD 3 CN at 25°C on 400 and 600 MHz Varian Inova spectrometers equipped with 5 mm PFG triple-resonance probes, unless otherwise stated. Assignments of 1 H and 13 C resonances were carried out using standard 2D NMR techniques.…”

“…[26,27] Two isomers may be formed in the intramolecular reactions. However, the transformation of 3 into the corresponding imidazolidinone compound took place with complete stereoselectivity, resulting in the formation of (2R)-6 in which the pentitolyl residue and hydroxybenzyl group have a trans arrangement and C2 of the imidazolidinone ring has the R configuration.…”

The early glycation products of the Maillard reaction: mass spectrometric characterization of novel imidazolidinones derived from an opioid pentapeptide and glucose

“…To investigate the early glycation products, in our recent studies we used carbohydrate‐peptide esters in which the sugar moiety ( D ‐glucose, D ‐mannose, or D ‐galactose) is linked through its C‐6 hydroxy group to the C‐terminal carboxy group of the endogenous opioid pentapeptide leucine‐enkephalin (H‐Tyr‐Gly‐Gly‐Phe‐Leu‐OH) as model compounds for the study of the Maillard reaction in vitro 12–14. We found for the first time that, depending on the reaction conditions, in addition to Amadori rearrangement, an alternative pathway for the carbohydrate‐induced modification of peptides is possible, yielding hexose‐related imidazolidinones 13,. 14 These results point to the possibility that, depending on the physiological environment, similar carbohydrate‐related imidazolidinones may also be generated as products of the early stage of the Maillard reaction in vivo .…”