Influence of glycation on cis/trans isomerization and tautomerization in novel morphiceptin-related Amadori compounds.
The influence of N-glycation of the N-terminus on amide bond stereochemistry and tautomeric distribution has been explored via the synthesis and NMR analysis of novel N-(1-deoxy-D-fructos-1-yl) derivatives (Amadori compounds) of the exogenous, milk derived, opioid tetrapeptide morphiceptin (H-Tyr-Pro-Phe-Pro-NH2). NMR analysis of the protected Amadori compounds revealed the presence of four configurational isomers in DMSO solution arising from cis/trans isomerization about Tyr1-Pro2 and Phe3-Pro4 peptide bonds. Comparison of the data obtained for protected Amadori compounds with those obtained for morphiceptin showed that equilibrium fraction of all-trans isomers in N-glycated peptide derivatives was smaller than in the parent peptide compound. Spectroscopic investigation of unprotected morphiceptin-related Amadori compound revealed the presence of multiple conformers in solution due to cis/trans isomerization of the peptide backbone and tautomerization of the sugar moiety. The equilibrium composition in DMSO is markedly shifted towards furanose forms, amounting to two-thirds of the mixture. The estimated equilibrium of the tautomeric forms in water solution revealed the beta-pyranose form as the major tautomer (66%).
Zigrović
I
I
Department of Organic Chemistry and Biochemistry, Ruder Bosković Institute, Zagreb, Croatia.
Kidric
J
J
Horvat
S
S
D000700:Analgesics / Q000737:chemistry; D000818:Animals; D004723:Endorphins / Q000737:chemistry*; D005947:Glucose / Q000737:chemistry*; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D008892:Milk / Q000737:chemistry; D015394:Molecular Structure
D000700:Analgesics; D004723:Endorphins; C028889:morphiceptin; D005947:Glucose