Formation of arginine modifications in a model system of Nα-tert-butoxycarbonyl (Boc)-arginine with methylglyoxal.
The present study deals with the mechanistic reaction pathway of the α-dicarbonyl compound methylglyoxal with the guanidino group of arginine. Eight products were formed from the reaction of methylglyoxal with N(α)-tert-butoxycarbonyl (Boc)-arginine under physiological conditions (pH 7.4 and 37 °C). Isolation and purification of substances were achieved using cation-exchange chromatography and preparative high-performance liquid chromatography (HPLC). Structures were verified by nuclear magnetic resonance (NMR) and high-resolution mass spectrometry. 2-Amino-5-(2-amino-4-hydro-4-methyl-5-imidazolinone-1-yl)pentanoic acid (3) was determined as the key intermediate precursor within the total reaction scheme. Kinetic studies identified N(δ)-(5-methyl-4-oxo-5-hydroimidazolinone-2-yl)-L-ornithine and N(7)-carboxyethylarginine as thermodynamically more stable products from compound 3. Further mechanistic investigations revealed an acidic hydrogen at C-8 of compound 3 to trigger aldol condensations. This reactivity of compound 3 allowed for the addition of another molecule of methylglyoxal to form products, such as N(δ)-(4-carboxy-4,6-dimethyl-5,6-dihydroxy-1,4,5,6-tetrahydropyrimidine-2-yl)-l-ornithine and argpyrimidine.
Institute of Chemistry, Food Chemistry, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany.
Antje
A
Klöpfer
Robert
R
Spanneberg
Marcus A
MA
Glomb
D001120:Arginine / Q000031:analogs & derivatives* / Q000737:chemistry*; D005503:Food Additives / Q000737:chemistry*; D007700:Kinetics; D008956:Models, Chemical; D011765:Pyruvaldehyde / Q000737:chemistry*
D005503:Food Additives; C107315:tert-butyloxycarbonyl-arginine; D011765:Pyruvaldehyde; D001120:Arginine