N-Terminal pyrazinones: a new class of peptide-bound advanced glycation end-products |
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Authors: | R Krause J Kühn I Penndorf K Knoll T Henle |
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Institution: | (1) Department of Pediatrics, University of Vienna, Vienna, Austria, AT;(2) Center for Medical Genomics, F. Hoffmann-La Roche, Basel, Switzerland, CH |
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Abstract: | Summary. The reaction of peptide Gly-Ala-Phe with the -dicarbonyl compounds glyoxal and methylglyoxal was studied under physiological conditions (pH=7.4, 37°C). Using HPLC with UV and fluorescence detection, a rapid derivatization of the peptide and the concomitant formation of well-defined products were observed. The products, which showed characteristic UV absorbance ( max=320 to 340 nm) and fluorescence ( ex=330 to 340 nm, em=395 to 405 nm), were identified by ESI-MS and NMR spectroscopic analysis as the N-terminally pyrazinone-modified peptides I (N-2-(2-oxo-2H-pyrazin-1-yl)-propyl]-phenylalanine) and II (N-2-(5-methyl-2-oxo-2H-pyrazin-1-yl)-propionyl]-phenylalanine). Model experiments revealed that the reactivity of the N-termini of peptides towards a derivatization by glyoxal is in the same order of magnitude as that of arginine, which generally is attributed as main target for -dicarbonyl compounds in proteins. Incubation of insulin with glyoxal proved the protein-bound formation of pyrazinones, with the N-terminus of the B-chain as the main target. According to these results, we conclude that N-terminal pyrazinones represent a new type of advanced glycation end-products (AGEs) with significance for biological systems and foods. |
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Keywords: | : Glycation – Maillard reaction – Pyrazinone – Advanced glycation end-product (AGE) – Glyoxal – Methylglyoxal – Insulin |
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