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Study of Degradation Pathways of Amadori Compounds Obtained by Glycation of Opioid Pentapeptide and Related Smaller Fragments: Stability, Reactions and Spectroscopic Properties

Reactions between biological amines and reducing sugars (the Maillard reaction) are among the most important of the chemical and oxidative changes occuring in biological systems that contribute to the formation of a complex family of rearranged and dehydrated covalent adducts that have been implicated in the pathogenesis of human diseases. In this study chemistry of the Maillard reactions was studied in four model systems containing fructosamines (Amadori compounds) obtained from the endogenous opioid pentapeptide leucine-enkephalin (Tyr-Gly-Gly-Phe-Leu), leucine-enkephalin methyl ester, structurally related tripeptide (Tyr-Gly-Gly), or from amino acid (Tyr). The degradation of model compounds as well as their ability to develop Maillard fluorescence was investigated under oxidative conditions in methanol and phosphate buffer pH 7.4 at two different temperatures (37 oC and 70 oC). At 37 oC, glycated leucine-enkephalin degraded slowly in methanol (t1/2  13 days) and phosphate buffer (t1/2  9 days) producing parent peptide compound as a major product throughout a 3-week incubation period. Whereas fluorescence slowly increased over time at 37 oC, incubations off all studied Amadori compounds at 70 oC resulted in rapid appearance of brown color and sharp increase in AGE (advanced glycation end products)-associated fluorescence (excitation 320 nm/emmision 420 nm) as well as in distinctly higher amounts of fragmentation products. The obtained data indicated that the shorter the peptide chain the more degradation products were formed. These studies have also helped to identify a new chemical transformation of the peptide backbone in the Maillard reaction that lead to  -scission of N-terminal tyrosine side chain and p-hydroxybenzaldehyde formation under both aqueous and non aqueous conditions.

AGE; Amadori; enkephalin; fluorescence; glycation; Maillard; opioid

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