Isolation, purification and characterization of histidino-threosidine, a novel Maillard reaction protein crosslink from threose, lysine and histidine

Abstract

We isolated a novel acid-labile yellow chromophore from the incubation of lysine, histidine and Dthreose and identified its chemical structure by one and two-dimensional 1 H and DEPT NMR spectroscopy combined with LC-tandem mass spectrometry. This new cross-link exhibits a UV absorbance maximum at 305 nm and a molecular mass of 451 Da. The proposed structure is 2-amino-5-(3-((4-(2-amino-2-carboxyethyl)-1H-imidazol-1-yl)methyl)-4-(1,2-dihydroxyethyl)-2-formyl-1H-pyrrol-1-yl)pentatonic acid, a cross-link between lysine and histidine with addition of two threose molecules. It was in part deduced and confirmed through synthesis of the analogous compound from n-butylamine, imidazole and D-threose. We assigned the compound the trivial name histidino-threosidine. Systemic incubation revealed that histidino-threosidine can be formed in low amounts from fructose, glyceraldehyde, methylglyoxal, glycolaldehyde, ascorbic acid, and dehydroascorbic acid, but at a much higher yield with degradation products of ascorbic acid, i.e. threose, erythrose, and erythrulose. Bovine lens protein incubated with 10 and 50 mM threose for two weeks yielded 560 and 2840 pmol/mg histidino-threosidine. Histidino-threosidine is to our knowledge the first Maillard reaction product known to involve histidine in a crosslink.

Non‐enzymatic glycation and glycoxidation protein products in foods and diseases: An interconnected, complex scenario fully open to innovative proteomic studies

“…Most of the linear or cross‐linked AGE derivatives reported in Figure were initially discovered by LC‐MS‐, GC‐MS‐, or LC‐ESI‐MS/MS‐based procedures, which were developed ad hoc and applied to the analysis of liquid foods, biological fluids (urine and plasma), or protein hydrolysates from solid (pharmaceutical, food, or tissue) samples previously subjected to acid or extensive enzymatic hydrolysis. Thus, different methods for partial and/or concomitant detection of these compounds were developed (Nakamura, Nakazawa, & Ienaga, ; Niwa et al, ; Odani et al, ; Glomb & Pfahler, ; Biemel et al, ; Glomb, Rosch, & Nagaraj, ; Odani et al, ; Biemel, Friedl, & Lederer, ; Tessier et al, ; Thornalley et al, ; Sell & Monnier, ; Teerlink et al, ; Sell et al, ; Dai et al, ; Schettgen et al, ; Assar et al, ; Delatour et al, ; Han et al, ; Henning et al, ; Nemet, Strauch, & Monnier, ; Sroga et al, ; Willett et al, ). Some AGEs, for example, dihydroxyimidazolines and hydroimidazolones, are not stable to extensive acid hydrolysis and were only detected under specific conditions.…”

“…When GC‐SIM experiments were performed, pre‐column derivatization to generate the corresponding trifluoroacetyl methyl esters or the N (O)‐ tert ‐butyldimethylsilyl derivatives was generally used (Glomb, Rosch, & Nagaraj, ; Hasenkopf et al, ; Pamplona et al, ; Fan et al, ; Fan et al, ; Wellner, Huettl, & Henle, ). Recent introduction of LC‐ESI‐MS/MS with multiple reaction monitoring (MRM) procedures, concurrent fluorescence detection and use of isotopically labeled internal standards allowed concomitant detection of FL, CEL, CML, CMA, PYR, GOLD, MOLD, DOLD, G‐H1, MG‐H1, MG‐H2, 3DG‐H1, 3DG‐H2, 3DG‐H3, RPYR, and PENT in biological samples from subjects under various pathophysiological conditions (Ahmed et al, ; Thornalley et al, ; Dai et al, ; Ni et al, ; Fan et al, ; Rabbani et al, ; Nemet, Strauch, & Monnier, ; Perkins et al, ) as well as in food products (Ahmed et al, ; Hegele, Buetler, & Delatour, ; Assar et al, ; Delatour et al, ; Zhang et al, ). Because of their stability to acid conditions, CML and pentosidine are generally the most frequently measured AGEs.…”

Assessment of Feasibility of Maillard Reaction between Baclofen and Lactose by Liquid Chromatography and Tandem Mass Spectrometry, Application to Pre Formulation Studies

“…Nowadays, mass spectrometry (MS) has been adopted by many researchers attempting to reveal the details of Maillard chemistry (9,(15)(16)(17)(18). Whereas traditional mass analysis would provide the fragment ions resulting from all compounds contained within a sample, tandem mass spectrometry provides information regarding the fragment ions that originate from a single molecular ion (9).…”

Favored and disfavored pathways of protein crosslinking by glucose: glucose lysine dimer (GLUCOLD) and crossline versus glucosepane

“…One additional signal at 5.01 ppm in 1 H NMR spectrum ( H -1′) showed in COSY spectrum coupling with proton at 3.60 ppm, while in HSQC spectrum correlation with C-atom at 62.5 ppm ( C -1′). By analogy with the C HOH signals in crossline, in which the sugar portion is directly bound on the aromatic ring and has similar chemical shifts [5.64 ppm ( 1 H) and 67.3 ppm ( 13 C)] (Nakamura et al 1992), as well as in vesperlysine C [4.97 ppm ( 1 H) and 61.5 ppm ( 13 C)] (Nakamura et al 1997), in GA-pyridine [4.81 ppm ( 1 H) and 58.0 ppm ( 13 C)] (Nagai et al 2002) and histidino-threosidine [4.70 ppm ( 1 H) and 66.0 ppm ( 13 C)] (Dai et al 2007), we propose that the sugar part of the structure is directly bound to the imidazolium ring. Other proton signals between 0.5 and 1.7 ppm together with carbon signals between 20 and 30 ppm were assigned as aliphatic chains of ε -amino caproic acid.…”