Glycation of a lysine-containing tetrapeptide by d-glucose and d-fructose—influence of different reaction conditions on the formation of Amadori/Heyns products

Jakas, Andreja; Katić, Anja; Bionda, Nina; Horvat, Štefica

doi:10.1016/j.carres.2008.07.003

Cited by 34 publications

(24 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This approach was also applied to synthesize d -ribose and d -fructose-modified peptides to study their fragmentation behavior (Frolov et al 2006a ). However, poor yields were reported for fructation, which was also true for other sequences (Jakas et al 2008 ). Similarly, the protocol reported by Heyns et al (Heyns and Noack 1962 ) provided also low yields of fructated hippuryl-lysine using anhydrous conditions in DMSO at 75 °C (Krause et al 2008 ).…”

Section: Introductionmentioning

confidence: 81%

Solid-phase synthesis of d-fructose-derived Heyns peptides utilizing Nα-Fmoc-Lysin[Nε-(2-deoxy-d-glucos-2-yl),Nε-Boc]-OH as building block

et al. 2021

View full text Add to dashboard Cite

Aldoses and ketoses can glycate proteins yielding isomeric Amadori and Heyns products, respectively. Evidently, d-fructose is more involved in glycoxidation than d-glucose favoring the formation of advanced glycation endproducts (AGEs). While Amadori products and glucation have been studied extensively, the in vivo effects of fructation are largely unknown. The characterization of isomeric Amadori and Heyns peptides requires sufficient quantities of pure peptides. Thus, the glycated building block Nα-Fmoc-Lys[Nε-(2-deoxy-d-glucos-2-yl),Nε-Boc]-OH (Fmoc-Lys(Glc,Boc)-OH), which was synthesized in two steps starting from unprotected d-fructose and Fmoc-l-lysine hydrochloride, was site-specifically incorporated during solid-phase peptide synthesis. The building block allowed the synthesis of a peptide identified in tryptic digests of human serum albumin containing the reported glycation site at Lys233. The structure of the glycated amino acid derivatives and the peptide was confirmed by mass spectrometry and NMR spectroscopy. Importantly, the unprotected sugar moiety showed neither notable epimerization nor undesired side reactions during peptide elongation, allowing the incorporation of epimerically pure glucosyllysine. Upon acidic treatment, the building block as well as the resin-bound peptide formed one major byproduct due to incomplete Boc-deprotection, which was well separated by reversed-phase chromatography. Expectedly, the tandem mass spectra of the fructated amino acid and peptide were dominated by signals indicating neutral losses of 18, 36, 54, 84 and 96 m/z-units generating pyrylium and furylium ions.

show abstract

Section: Introductionmentioning

confidence: 81%

Solid-phase synthesis of d-fructose-derived Heyns peptides utilizing Nα-Fmoc-Lysin[Nε-(2-deoxy-d-glucos-2-yl),Nε-Boc]-OH as building block

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In addition, one extreme case of purification has also been reported, wherein, after Heyns reaction of N‐hippurly lysine with fructose, carboxypeptidase B was utilized to cleave hippuryl lysine and subsequent usage of preparative HPLC to accomplish pure Heyns peptide [11] . Another key approach developed to accomplish glycopeptides encompassed reductive amination of protected aldoketose/ketoaldose with peptide in presence of sodium cyanobrohydride resulting in Amadori/Heyns peptides [12–14] . This approach requires many demanding steps consisting of protection of sugar, oxidation, before reaction with peptide.…”

Section: Introductionmentioning

confidence: 99%

“…[11] Another key approach developed to accomplish glycopeptides encompassed reductive amination of protected aldoketose/ketoaldose with peptide in presence of sodium cyanobrohydride resulting in Amadori/Heyns peptides. [12][13][14] This approach requires many demanding steps consisting of protection of sugar, oxidation, before reaction with peptide. The entire synthetic protocol is not practical and quantitative.…”

Section: Introductionmentioning

confidence: 99%

Lewis‐Acid‐Catalyzed Synthesis of Amadori and Heyns Dipeptides

2020

View full text Add to dashboard Cite

Amadori and Heyns reactions are milestone reactions of carbohydrate chemistry. There have been little efforts in transforming these rearrangement reactions to useful catalytic tools. We demonstrate herein, synthesis of Amadori and Heyns dipeptides via Lewis acid-catalysis. The accomplished catalytic Amadori and Heyns synthesis is devoid of protection and deprotection steps either for dipeptides or for reducing sugar. By the developed catalytic method we achieved, tagatose Amadori dipeptides via reaction of D-galactose with dipeptides including L-alanyl glycine, L-alanyl-L-alanine, L-alanyl-L-glutamine, glycyl-L-phenylalanine, L-leucyl glycine, L-pheynylalanyl-L-valine in excellent yield. In addition, Heyns dipeptides were also achieved by employing D-fructose and dipeptides consisting of L-alanyl glycine, L-alanyl-L-alanine, L-alanyl-L-glutamine, glycyl-L-phenylalanine, L-leucyl glycine. The realized Lewis acid mediated catalytic method is practical, quantitative, and avoids chromatographic separation techniques.

show abstract

“…A limited number of studies have been conducted on the reactivity of peptides in the Maillard reaction. The majority of these studies have focused on the free amino acid, glycine homopolymer in model systems representing either physiological [15,16,17] or food-related conditions [17]. Although their results can represent the reactivity of free amino acids, di-, tri- and tetrapeptides in the Maillard reaction [18], the reactivity in their case has been defined as the rate in which glucose has been converted in the early-phase of the Maillard reaction, only the Schiff base formation and Amadori rearrangement reaction have been involved, and the products at the final stage of the Maillard reaction have not been mentioned.…”

Section: Introductionmentioning

confidence: 99%

Formation of Peptide Bound Pyrraline in the Maillard Model Systems with Different Lys-Containing Dipeptides and Tripeptides

Liang

et al. 2016

Molecules

View full text Add to dashboard Cite

Peptide-bound advanced glycation end-products (peptide-bound AGEs) can be formed when peptides are heated with reducing saccharides. Pyrraline is the one of most commonly studied AGEs in foods, but the relative importance of the precursor peptide structure is uncertain. In the present study, model systems were prepared by heating peptides with glucose from 60˝C to 220˝C for up to 65 min, and the amounts of peptide-bound pyrraline formed were monitored to evaluate the effect of the neighboring amino acids on the peptide-bound pyrraline formation. The physico-chemical properties were introduced to explore the quantitative structure-reactivity relationships between physicochemical properties and peptide bound formation. 3-DG content in dipeptide-glucose model system was higher than that in the corresponding tripeptide-glucose model systems. Dipeptides produced higher amounts of peptide-bound pyrraline than the corresponding tripeptides. The peptide-bound pyrraline and 3-DG production were influenced by the physico-chemical properties of the side chain of amino acids adjacent to Lys in the following order: Lys-Leu/glucose > Lys-Ile/glucose > Lys-Val/ glucose > Lys-Thr/glucose > Lys-Ser/glucose > Lys-Ala/ glucose > Lys-Gly/glucose; Lys-Leu-Gly/glucose > Lys-Ile-Gly/glucose > Lys-Val-Gly/glucose > Lys-Thr-Gly/glucose > Lys-Ser-Gly/glucose > Lys-Ala-Gly/glucose > Lys-Gly-Gly/glucose. For the side chain of amino acids adjacent to Lys in dipeptides, residue volume, polarizability, molecular volume and localized electrical effect were positively related to the yield of peptide bound pyrraline, while hydrophobicity and pK b were negatively related to the yield of peptide bound pyrraline. In terms of side chain of amino acid adjacent to Lys in tripeptides, a similar result was observed, except hydrophobicity was positively related to the yield of peptide bound pyrraline.

show abstract

Glycation of a lysine-containing tetrapeptide by d-glucose and d-fructose—influence of different reaction conditions on the formation of Amadori/Heyns products

Cited by 34 publications

References 22 publications

Solid-phase synthesis of d-fructose-derived Heyns peptides utilizing Nα-Fmoc-Lysin[Nε-(2-deoxy-d-glucos-2-yl),Nε-Boc]-OH as building block

Solid-phase synthesis of d-fructose-derived Heyns peptides utilizing Nα-Fmoc-Lysin[Nε-(2-deoxy-d-glucos-2-yl),Nε-Boc]-OH as building block

Lewis‐Acid‐Catalyzed Synthesis of Amadori and Heyns Dipeptides

Formation of Peptide Bound Pyrraline in the Maillard Model Systems with Different Lys-Containing Dipeptides and Tripeptides

Contact Info

Product

Resources

About